The ceramide synthase (CERS/LASS) family: Functions involved in cancer progression

go back to reference J.C. Jiang, P.A. Kirchman, M. Zagulski, J. Hunt, S.M. Jazwinski, Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human. Genome Res. 8, 1259–1272 (1998)PubMed J.C. Jiang, P.A. Kirchman, M. Zagulski, J. Hunt, S.M. Jazwinski, Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human. Genome Res. 8, 1259–1272 (1998)PubMed

go back to reference H. Pan, W.X. Qin, K.K. Huo, D.F. Wan, Y. Yu, Z.G. Xu, Q.D. Hu, K.T. Gu, X.M. Zhou, H.Q. Jiang, P.P. Zhang, Y. Huang, Y.Y. Li, J.R. Gu, Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1. Genomics 77, 58–64 (2001) H. Pan, W.X. Qin, K.K. Huo, D.F. Wan, Y. Yu, Z.G. Xu, Q.D. Hu, K.T. Gu, X.M. Zhou, H.Q. Jiang, P.P. Zhang, Y. Huang, Y.Y. Li, J.R. Gu, Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1. Genomics 77, 58–64 (2001)

go back to reference Y. Mizutani, A. Kihara, Y. Igarashi, LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro) ceramide synthase with relatively broad substrate specificity. Biochem. J. 398, 531–538 (2006)PubMedPubMedCentral Y. Mizutani, A. Kihara, Y. Igarashi, LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro) ceramide synthase with relatively broad substrate specificity. Biochem. J. 398, 531–538 (2006)PubMedPubMedCentral

go back to reference C. Riebeling, J.C. Allegood, E. Wang, A.H. Merrill Jr., A.H. Futerman, Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors. J. Biol. Chem. 278, 43452–43459 (2003)PubMed C. Riebeling, J.C. Allegood, E. Wang, A.H. Merrill Jr., A.H. Futerman, Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors. J. Biol. Chem. 278, 43452–43459 (2003)PubMed

go back to reference S. Lahiri, A.H. Futerman, LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl-CoA as acyl donor. J. Biol. Chem. 280, 33735–33738 (2005)PubMed S. Lahiri, A.H. Futerman, LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl-CoA as acyl donor. J. Biol. Chem. 280, 33735–33738 (2005)PubMed

go back to reference Y. Mizutani, A. Kihara, Y. Igarashi, Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem. J. 390, 263–271 (2005)PubMedPubMedCentral Y. Mizutani, A. Kihara, Y. Igarashi, Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem. J. 390, 263–271 (2005)PubMedPubMedCentral

go back to reference K. Kitatani, J. Idkowiak-Baldys, Y.A. Hannun, The sphingolipid salvage pathway in ceramide metabolism and signaling. Cell. Signal. 20, 1010–1018 (2008)PubMed K. Kitatani, J. Idkowiak-Baldys, Y.A. Hannun, The sphingolipid salvage pathway in ceramide metabolism and signaling. Cell. Signal. 20, 1010–1018 (2008)PubMed

go back to reference G. Tettamanti, Ganglioside/glycosphingolipid turnover: new concepts. Glycoconj. J. 20, 301–317 (2004)PubMed G. Tettamanti, Ganglioside/glycosphingolipid turnover: new concepts. Glycoconj. J. 20, 301–317 (2004)PubMed

go back to reference M. Sugiura, K. Kono, H. Liu, T. Shimizugawa, H. Minekura, S. Spiegel, T. Kohama, Ceramide kinase, a novel lipid kinase. Molecular cloning and functional characterization. J. Biol. Chem. 277, 23294–23300 (2002)PubMed M. Sugiura, K. Kono, H. Liu, T. Shimizugawa, H. Minekura, S. Spiegel, T. Kohama, Ceramide kinase, a novel lipid kinase. Molecular cloning and functional characterization. J. Biol. Chem. 277, 23294–23300 (2002)PubMed

go back to reference F.G. Tafesse, P. Ternes, J.C. Holthuis, The multigenic sphingomyelin synthase family. J. Biol. Chem. 281, 29421–29425 (2006)PubMed F.G. Tafesse, P. Ternes, J.C. Holthuis, The multigenic sphingomyelin synthase family. J. Biol. Chem. 281, 29421–29425 (2006)PubMed

go back to reference A. Mesika, S. Ben-Dor, E.L. Laviad, A.H. Futerman, A new functional motif in hox domain-containing ceramide synthases: identification of a novel region flanking the hox and TLC domains essential for activity. J. Biol. Chem. 282, 27366–27373 (2007)PubMed A. Mesika, S. Ben-Dor, E.L. Laviad, A.H. Futerman, A new functional motif in hox domain-containing ceramide synthases: identification of a novel region flanking the hox and TLC domains essential for activity. J. Biol. Chem. 282, 27366–27373 (2007)PubMed

go back to reference D. Görlich, T.A. Rapoport, Protein translocation into proteoliposomes reconstituted from purified components of the endoplasmic reticulum membrane. Cell 75, 615–630 (1993)PubMed D. Görlich, T.A. Rapoport, Protein translocation into proteoliposomes reconstituted from purified components of the endoplasmic reticulum membrane. Cell 75, 615–630 (1993)PubMed

go back to reference R. Jennemann, M. Rabionet, K. Gorgas, S. Epstein, A. Dalpke, U. Rothermel, A. Bayerle, F. van der Hoeven, S. Imgrund, J. Kirsch, W. Nickel, K. Willecke, H. Riezman, H.J. Gröne, R. Sandhoff. Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum. Mol. Genet. 21, 586–608 (2012)PubMed R. Jennemann, M. Rabionet, K. Gorgas, S. Epstein, A. Dalpke, U. Rothermel, A. Bayerle, F. van der Hoeven, S. Imgrund, J. Kirsch, W. Nickel, K. Willecke, H. Riezman, H.J. Gröne, R. Sandhoff. Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum. Mol. Genet. 21, 586–608 (2012)PubMed

go back to reference J.W. Park, W.J. Park, A.H. Futerman, Ceramide synthases as potential targets for therapeutic intervention in human diseases. Biochim. Biophys. Acta 1841, 671–681 (2014)PubMed J.W. Park, W.J. Park, A.H. Futerman, Ceramide synthases as potential targets for therapeutic intervention in human diseases. Biochim. Biophys. Acta 1841, 671–681 (2014)PubMed

go back to reference R. Tidhar, I.D. Zelnik, G. Volpert, S. Ben-Dor, S. Kelly, A.H. Merrill Jr., A.H. Futerman, Eleven residues determine the acyl chain specificity of ceramide synthases. J. Biol. Chem. 293, 9912–9921 (2018)PubMedPubMedCentral R. Tidhar, I.D. Zelnik, G. Volpert, S. Ben-Dor, S. Kelly, A.H. Merrill Jr., A.H. Futerman, Eleven residues determine the acyl chain specificity of ceramide synthases. J. Biol. Chem. 293, 9912–9921 (2018)PubMedPubMedCentral

go back to reference J.L. Kim, S. Ben-Dor, E. Rosenfeld-Gur, A.H. Futerman, A novel C-terminal DxRSDxE motif in ceramide synthases involved in dimer formation. J. Biol. Chem. 298, 101517 (2022)PubMed J.L. Kim, S. Ben-Dor, E. Rosenfeld-Gur, A.H. Futerman, A novel C-terminal DxRSDxE motif in ceramide synthases involved in dimer formation. J. Biol. Chem. 298, 101517 (2022)PubMed

go back to reference B.J. Pettus, M. Baes, M. Busman, Y.A. Hannun, P.P. Van Veldhoven, Mass spectrometric analysis of ceramide perturbations in brain and fibroblasts of mice and human patients with peroxisomal disorders. Rapid Commun. Mass. Spectrom. 18, 1569–1574 (2004)PubMed B.J. Pettus, M. Baes, M. Busman, Y.A. Hannun, P.P. Van Veldhoven, Mass spectrometric analysis of ceramide perturbations in brain and fibroblasts of mice and human patients with peroxisomal disorders. Rapid Commun. Mass. Spectrom. 18, 1569–1574 (2004)PubMed

go back to reference M. Levy, A.H. Futerman, Mammalian ceramide synthases. IUBMB Life 62, 347–356 (2010)PubMedPubMedCentral M. Levy, A.H. Futerman, Mammalian ceramide synthases. IUBMB Life 62, 347–356 (2010)PubMedPubMedCentral

go back to reference B. Wang, G. Shi, Y. Fu, X. Xu, Cloning and characterization of a LASS1-GDF1 transcript in rat cerebral cortex: conservation of a bicistronic structure. DNA Seq. 18, 92–103 (2007)PubMed B. Wang, G. Shi, Y. Fu, X. Xu, Cloning and characterization of a LASS1-GDF1 transcript in rat cerebral cortex: conservation of a bicistronic structure. DNA Seq. 18, 92–103 (2007)PubMed

go back to reference M. Meyers-Needham, S. Ponnusamy, S. Gencer, W. Jiang, R.J. Thomas, C.E. Senkal, B. Ogretmen, Concerted functions of HDAC1 and microRNA-574-5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells. EMBO Mol. Med. 4, 78–92 (2012)PubMedPubMedCentral M. Meyers-Needham, S. Ponnusamy, S. Gencer, W. Jiang, R.J. Thomas, C.E. Senkal, B. Ogretmen, Concerted functions of HDAC1 and microRNA-574-5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells. EMBO Mol. Med. 4, 78–92 (2012)PubMedPubMedCentral

go back to reference Z. Yang, G. Yan, L. Zheng, W. Gu, F. Liu, W. Chen, X. Cui, Y. Wang, Y. Yang, X. Chen, Y. Fu, X. Xu, YKT6, as a potential predictor of prognosis and immunotherapy response for oral squamous cell carcinoma, is related to cell invasion, metastasis, and CD8+ T cell infiltration. Oncoimmunology. 10, 1938890 (2021) Z. Yang, G. Yan, L. Zheng, W. Gu, F. Liu, W. Chen, X. Cui, Y. Wang, Y. Yang, X. Chen, Y. Fu, X. Xu, YKT6, as a potential predictor of prognosis and immunotherapy response for oral squamous cell carcinoma, is related to cell invasion, metastasis, and CD8⁺ T cell infiltration. Oncoimmunology. 10, 1938890 (2021)

go back to reference C.S. Lin, A.B. de Oliveira Santos, E.L. Silva, L.L. de Matos, R.A. Moyses, M.A. Kulcsar, F.R. Pinto, L.G. Brandão, C.R. Cernea, Tumor volume as an independent predictive factor of worse survival in patients with oral cavity squamous cell carcinoma. Head Neck 39, 960–964 (2017)PubMed C.S. Lin, A.B. de Oliveira Santos, E.L. Silva, L.L. de Matos, R.A. Moyses, M.A. Kulcsar, F.R. Pinto, L.G. Brandão, C.R. Cernea, Tumor volume as an independent predictive factor of worse survival in patients with oral cavity squamous cell carcinoma. Head Neck 39, 960–964 (2017)PubMed

go back to reference W. Chen, C. Wu, Y. Chen, Y. Guo, L. Qiu, Z. Liu, H. Sun, S. Chen, Z. An, Z. Zhang, Y. Li, L. Li, Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress. Int. J. Oral Sci. 13, 10 (2021)PubMedPubMedCentral W. Chen, C. Wu, Y. Chen, Y. Guo, L. Qiu, Z. Liu, H. Sun, S. Chen, Z. An, Z. Zhang, Y. Li, L. Li, Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress. Int. J. Oral Sci. 13, 10 (2021)PubMedPubMedCentral

go back to reference J. Wang, J. Zhang, D. Ma, X. Li, The potential role of CERS1 in autophagy through PI3K/AKT signaling pathway in hypophysoma. Technol. Cancer Res. Treat. 19, 1533033820977536 (2020)PubMedPubMedCentral J. Wang, J. Zhang, D. Ma, X. Li, The potential role of CERS1 in autophagy through PI3K/AKT signaling pathway in hypophysoma. Technol. Cancer Res. Treat. 19, 1533033820977536 (2020)PubMedPubMedCentral

go back to reference C.E. Senkal, S. Ponnusamy, M.J. Rossi, J. Bialewski, D. Sinha, J.C. Jiang, S.M. Jazwinski, Y.A. Hannun, B. Ogretmen, Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas. Mol. Cancer Ther. 6, 712–722 (2007)PubMed C.E. Senkal, S. Ponnusamy, M.J. Rossi, J. Bialewski, D. Sinha, J.C. Jiang, S.M. Jazwinski, Y.A. Hannun, B. Ogretmen, Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas. Mol. Cancer Ther. 6, 712–722 (2007)PubMed

go back to reference N. Mizushima, B. Levine, A.M. Cuervo, D.J. Klionsky, Autophagy fights disease through cellular self-digestion. Nature 451, 1069–1075 (2008)PubMedPubMedCentral N. Mizushima, B. Levine, A.M. Cuervo, D.J. Klionsky, Autophagy fights disease through cellular self-digestion. Nature 451, 1069–1075 (2008)PubMedPubMedCentral

go back to reference R.D. Sentelle, C.E. Senkal, W. Jiang, S. Ponnusamy, S. Gencer, S.P. Selvam, V.K. Ramshesh, Y.K. Peterson, J.J. Lemasters, Z.M. Szulc, J. Bielawski, B. Ogretmen, Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat. Chem. Biol. 8, 831–838 (2012)PubMedPubMedCentral R.D. Sentelle, C.E. Senkal, W. Jiang, S. Ponnusamy, S. Gencer, S.P. Selvam, V.K. Ramshesh, Y.K. Peterson, J.J. Lemasters, Z.M. Szulc, J. Bielawski, B. Ogretmen, Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat. Chem. Biol. 8, 831–838 (2012)PubMedPubMedCentral

go back to reference C.E. Senkal, S. Ponnusamy, J. Bielawski, Y.A. Hannun, B. Ogretmen, Antiapoptotic roles of ceramide-synthase-6-generated C16-ceramide via selective regulation of the ATF6/CHOP arm of ER-stress-response pathways. FASEB J. 24, 296–308 (2010)PubMedPubMedCentral C.E. Senkal, S. Ponnusamy, J. Bielawski, Y.A. Hannun, B. Ogretmen, Antiapoptotic roles of ceramide-synthase-6-generated C₁₆-ceramide via selective regulation of the ATF6/CHOP arm of ER-stress-response pathways. FASEB J. 24, 296–308 (2010)PubMedPubMedCentral

go back to reference F. Lan, Q. Qing, Q. Pan, M. Hu, H. Yu, X. Yue, Serum exosomal miR-301a as a potential diagnostic and prognostic biomarker for human glioma. Cell. Oncol. 41, 25–33 (2018) F. Lan, Q. Qing, Q. Pan, M. Hu, H. Yu, X. Yue, Serum exosomal miR-301a as a potential diagnostic and prognostic biomarker for human glioma. Cell. Oncol. 41, 25–33 (2018)

go back to reference X. Cheng, Z. Ren, Z. Liu, X. Sun, R. Qian, C. Cao, B. Liu, J. Wang, H. Wang, Y. Guo, Y. Gao, Cysteine cathepsin C: a novel potential biomarker for the diagnosis and prognosis of glioma. Cancer Cell. Int. 22, 53 (2022)PubMedPubMedCentral X. Cheng, Z. Ren, Z. Liu, X. Sun, R. Qian, C. Cao, B. Liu, J. Wang, H. Wang, Y. Guo, Y. Gao, Cysteine cathepsin C: a novel potential biomarker for the diagnosis and prognosis of glioma. Cancer Cell. Int. 22, 53 (2022)PubMedPubMedCentral

go back to reference N. Vanni, F. Fruscione, E. Ferlazzo, P. Striano, A. Robbiano, M. Traverso, T. Sander, A. Falace, E. Gazzerro, P. Bramanti, J. Bielawski, A. Fassio, C. Minetti, P. Genton, F. Zara, Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy. Ann. Neurol. 76, 206–212 (2014)PubMed N. Vanni, F. Fruscione, E. Ferlazzo, P. Striano, A. Robbiano, M. Traverso, T. Sander, A. Falace, E. Gazzerro, P. Bramanti, J. Bielawski, A. Fassio, C. Minetti, P. Genton, F. Zara, Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy. Ann. Neurol. 76, 206–212 (2014)PubMed

go back to reference Z. Wang, L. Wen, F. Zhu, Y. Wang, Q. Xie, Z. Chen, Y. Li, Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma. Oncotarget 8, 104022–104036 (2017)PubMedPubMedCentral Z. Wang, L. Wen, F. Zhu, Y. Wang, Q. Xie, Z. Chen, Y. Li, Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma. Oncotarget 8, 104022–104036 (2017)PubMedPubMedCentral

go back to reference K. Liu, Y. Shi, X. Guo, S. Wang, Y. Ouyang, M. Hao, D. Liu, L. Qiao, N. Li, J. Zheng, D. Chen, CHOP mediates ASPP2-induced autophagic apoptosis in hepatoma cells by releasing Beclin-1 from Bcl-2 and inducing nuclear translocation of Bcl-2. Cell. Death Dis. 5, e1323 (2014)PubMedPubMedCentral K. Liu, Y. Shi, X. Guo, S. Wang, Y. Ouyang, M. Hao, D. Liu, L. Qiao, N. Li, J. Zheng, D. Chen, CHOP mediates ASPP2-induced autophagic apoptosis in hepatoma cells by releasing Beclin-1 from Bcl-2 and inducing nuclear translocation of Bcl-2. Cell. Death Dis. 5, e1323 (2014)PubMedPubMedCentral

go back to reference W.H. Zhou, H. Fang, Q. Wu, X. Wang, R. Liu, F. Li, J. Xiao, L. Yuan, Z. Zhou, J. Ma, L. Wang, W. Zhao, H. You, J. Ju, J. Feng, C. Chen, Ilamycin E, a natural product of marine actinomycete, inhibits triple-negative breast cancer partially through ER stress-CHOP-Bcl-2. Int. J. Biol. Sci. 15, 1723–1732 (2019)PubMedPubMedCentral W.H. Zhou, H. Fang, Q. Wu, X. Wang, R. Liu, F. Li, J. Xiao, L. Yuan, Z. Zhou, J. Ma, L. Wang, W. Zhao, H. You, J. Ju, J. Feng, C. Chen, Ilamycin E, a natural product of marine actinomycete, inhibits triple-negative breast cancer partially through ER stress-CHOP-Bcl-2. Int. J. Biol. Sci. 15, 1723–1732 (2019)PubMedPubMedCentral

go back to reference R.L. Siegel, K.D. Miller, H.E. Fuchs, A. Jemal, Cancer statistics, 2022. CA Cancer J. Clin 72, 7–33 (2022)PubMed R.L. Siegel, K.D. Miller, H.E. Fuchs, A. Jemal, Cancer statistics, 2022. CA Cancer J. Clin 72, 7–33 (2022)PubMed

go back to reference Y. Wang, N. Wu, N. Jiang, Autophagy provides a conceptual therapeutic framework for bone metastasis from prostate cancer. Cell. Death Dis. 12, 909 (2021)PubMedPubMedCentral Y. Wang, N. Wu, N. Jiang, Autophagy provides a conceptual therapeutic framework for bone metastasis from prostate cancer. Cell. Death Dis. 12, 909 (2021)PubMedPubMedCentral

go back to reference Z.W. Zhao, L.L. Yang, J.S. Ji, L.Y. Zheng, S.J. Fang, J.L. Wang, Effects and mechanism of itraconazole on prostate cancer PC-3 cell apoptosis. Zhonghua Yi Xue Za Zhi 96, 3160–3163 (2016)PubMed Z.W. Zhao, L.L. Yang, J.S. Ji, L.Y. Zheng, S.J. Fang, J.L. Wang, Effects and mechanism of itraconazole on prostate cancer PC-3 cell apoptosis. Zhonghua Yi Xue Za Zhi 96, 3160–3163 (2016)PubMed

go back to reference H.X. Li, J. Zeng, K. Shen, PI3K/AKT/mTOR signaling pathway as a therapeutic target for ovarian cancer. Arch. Gynecol. Obstet. 290, 1067–1078 (2014)PubMed H.X. Li, J. Zeng, K. Shen, PI3K/AKT/mTOR signaling pathway as a therapeutic target for ovarian cancer. Arch. Gynecol. Obstet. 290, 1067–1078 (2014)PubMed

go back to reference J. Min, A. Mesika, M. Sivaguru, P.P. Van Veldhoven, H. Alexander, A.H. Futerman, S. Alexander, (Dihydro) ceramide synthase 1 regulated sensitivity to cisplatin is associated with the activation of p38 mitogen-activated protein kinase and is abrogated by sphingosine kinase 1. Mol. Cancer Res. 5, 801–812 (2007)PubMed J. Min, A. Mesika, M. Sivaguru, P.P. Van Veldhoven, H. Alexander, A.H. Futerman, S. Alexander, (Dihydro) ceramide synthase 1 regulated sensitivity to cisplatin is associated with the activation of p38 mitogen-activated protein kinase and is abrogated by sphingosine kinase 1. Mol. Cancer Res. 5, 801–812 (2007)PubMed

go back to reference Y. Baran, A. Salas, C.E. Senkal, U. Gunduz, J. Bielawski, L.M. Obeid, B. Ogretmen, Alterations of ceramide/sphingosine 1-phosphate rheostat involved in the regulation of resistance to imatinib-induced apoptosis in K562 human chronic myeloid leukemia cells. J. Biol. Chem. 282, 10922–10934 (2007)PubMed Y. Baran, A. Salas, C.E. Senkal, U. Gunduz, J. Bielawski, L.M. Obeid, B. Ogretmen, Alterations of ceramide/sphingosine 1-phosphate rheostat involved in the regulation of resistance to imatinib-induced apoptosis in K562 human chronic myeloid leukemia cells. J. Biol. Chem. 282, 10922–10934 (2007)PubMed

go back to reference J. Khaled, M. Kopsida, H. Lennernäs, F. Heindryckx, Drug resistance and endoplasmic reticulum stress in hepatocellular carcinoma. Cells 11, 632 (2022)PubMedPubMedCentral J. Khaled, M. Kopsida, H. Lennernäs, F. Heindryckx, Drug resistance and endoplasmic reticulum stress in hepatocellular carcinoma. Cells 11, 632 (2022)PubMedPubMedCentral

go back to reference A. Camgoz, E.B. Gencer, A.U. Ural, Y. Baran, Mechanisms responsible for nilotinib resistance in human chronic myeloid leukemia cells and reversal of resistance. Leuk. Lymphoma 54, 1279–1287 (2013)PubMed A. Camgoz, E.B. Gencer, A.U. Ural, Y. Baran, Mechanisms responsible for nilotinib resistance in human chronic myeloid leukemia cells and reversal of resistance. Leuk. Lymphoma 54, 1279–1287 (2013)PubMed

go back to reference T. Sassa, T. Hirayama, A. Kihara, Enzyme activities of the ceramide synthases CERS2-6 are regulated by phosphorylation in the C-terminal region. J. Biol. Chem. 291, 7477–7487 (2016)PubMedPubMedCentral T. Sassa, T. Hirayama, A. Kihara, Enzyme activities of the ceramide synthases CERS2-6 are regulated by phosphorylation in the C-terminal region. J. Biol. Chem. 291, 7477–7487 (2016)PubMedPubMedCentral

go back to reference R. Gopal, K. Selvarasu, P.P. Pandian, K. Ganesan, Integrative transcriptome analysis of liver cancer profiles identifies upstream regulators and clinical significance of ACSM3 gene expression. Cell. Oncol. 40, 219–233 (2017) R. Gopal, K. Selvarasu, P.P. Pandian, K. Ganesan, Integrative transcriptome analysis of liver cancer profiles identifies upstream regulators and clinical significance of ACSM3 gene expression. Cell. Oncol. 40, 219–233 (2017)

go back to reference A. Bickert, P. Kern, M. Van Uelft, S. Herresthal, T. Ulas, K. Gutbrod, B. Breiden, J. Degen, K. Sandhoff, J.L. Schultze, P. Dörmann, D. Hartmann, R. Bauer, K. Willecke, Inactivation of ceramide synthase 2 catalytic activity in mice affects transcription of genes involved in lipid metabolism and cell division. Biochim. Biophys. Acta Mol. Cell. Biol. Lipids 1863, 734–749 (2018)PubMed A. Bickert, P. Kern, M. Van Uelft, S. Herresthal, T. Ulas, K. Gutbrod, B. Breiden, J. Degen, K. Sandhoff, J.L. Schultze, P. Dörmann, D. Hartmann, R. Bauer, K. Willecke, Inactivation of ceramide synthase 2 catalytic activity in mice affects transcription of genes involved in lipid metabolism and cell division. Biochim. Biophys. Acta Mol. Cell. Biol. Lipids 1863, 734–749 (2018)PubMed

go back to reference Y. Yang, X. Yang, L. Li, G. Yang, X. Ouyang, J. Xiang, T. Zhang, X. Min, LASS2 inhibits proliferation and induces apoptosis in HepG2 cells by affecting mitochondrial dynamics, the cell cycle and the nuclear factor-κB pathways. Oncol. Rep. 41, 3005–3014 (2019)PubMed Y. Yang, X. Yang, L. Li, G. Yang, X. Ouyang, J. Xiang, T. Zhang, X. Min, LASS2 inhibits proliferation and induces apoptosis in HepG2 cells by affecting mitochondrial dynamics, the cell cycle and the nuclear factor-κB pathways. Oncol. Rep. 41, 3005–3014 (2019)PubMed

go back to reference D. Gu, H. Jin, G. Jin, C. Wang, N. Wang, F. Hu, Q. Luo, W. Chu, M. Yao, W. Qin, The asialoglycoprotein receptor suppresses the metastasis of hepatocellular carcinoma via LASS2-mediated inhibition of V-ATPase activity. Cancer Lett. 379, 107–116 (2016)PubMed D. Gu, H. Jin, G. Jin, C. Wang, N. Wang, F. Hu, Q. Luo, W. Chu, M. Yao, W. Qin, The asialoglycoprotein receptor suppresses the metastasis of hepatocellular carcinoma via LASS2-mediated inhibition of V-ATPase activity. Cancer Lett. 379, 107–116 (2016)PubMed

go back to reference T. Pani, K. Rajput, A. Kar, U. Dasgupta, Alternative splicing of CERS2 promotes cell proliferation and migration in luminal B subtype breast cancer cells. Oncoscience 8, 50–52 (2021)PubMedPubMedCentral T. Pani, K. Rajput, A. Kar, U. Dasgupta, Alternative splicing of CERS2 promotes cell proliferation and migration in luminal B subtype breast cancer cells. Oncoscience 8, 50–52 (2021)PubMedPubMedCentral

go back to reference R. Erez-Roman, R. Pienik, A.H. Futerman, Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression. Biochem. Biophys. Res. Commun. 391, 219–223 (2010)PubMed R. Erez-Roman, R. Pienik, A.H. Futerman, Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression. Biochem. Biophys. Res. Commun. 391, 219–223 (2010)PubMed

go back to reference S.H. Fan, Y.Y. Wang, J. Lu, Y.L. Zheng, D.M. Wu, Z.F. Zhang, Q. Shan, B. Hu, M.Q. Li, W. Cheng, CERS2 suppresses tumor cell invasion and is associated with decreased V-ATPase and MMP-2/MMP-9 activities in breast cancer. J. Cell. Biochem. 116, 502–513 (2015)PubMed S.H. Fan, Y.Y. Wang, J. Lu, Y.L. Zheng, D.M. Wu, Z.F. Zhang, Q. Shan, B. Hu, M.Q. Li, W. Cheng, CERS2 suppresses tumor cell invasion and is associated with decreased V-ATPase and MMP-2/MMP-9 activities in breast cancer. J. Cell. Biochem. 116, 502–513 (2015)PubMed

go back to reference S. Fan, Y. Niu, N. Tan, Z. Wu, Y. Wang, H. You, R. Ke, J. Song, Q. Shen, W. Wang, G. Yao, H. Shu, H. Lin, M. Yao, Z. Zhang, J. Gu, W. Qin, LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor microenvironment through inhibiting activity of V-ATPase proton pump. Oncogene 32, 1682–1690 (2013)PubMed S. Fan, Y. Niu, N. Tan, Z. Wu, Y. Wang, H. You, R. Ke, J. Song, Q. Shen, W. Wang, G. Yao, H. Shu, H. Lin, M. Yao, Z. Zhang, J. Gu, W. Qin, LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor microenvironment through inhibiting activity of V-ATPase proton pump. Oncogene 32, 1682–1690 (2013)PubMed

go back to reference S. Liu, X. Chen, T. Lin, Lymphatic metastasis of bladder cancer: molecular mechanisms, diagnosis and targeted therapy. Cancer Lett. 505, 13–23 (2021)PubMed S. Liu, X. Chen, T. Lin, Lymphatic metastasis of bladder cancer: molecular mechanisms, diagnosis and targeted therapy. Cancer Lett. 505, 13–23 (2021)PubMed

go back to reference H. He, S. Wu, K. Ai, R. Xu, Z. Zhong, Y. Wang, L. Zhang, X. Zhao, X. Zhu, LncRNA ZNF503-AS1 acts as a tumor suppressor in bladder cancer by up-regulating Ca2+ concentration via transcription factor GATA6. Cell. Oncol. 44, 219–233 (2021) H. He, S. Wu, K. Ai, R. Xu, Z. Zhong, Y. Wang, L. Zhang, X. Zhao, X. Zhu, LncRNA ZNF503-AS1 acts as a tumor suppressor in bladder cancer by up-regulating Ca²⁺ concentration via transcription factor GATA6. Cell. Oncol. 44, 219–233 (2021)

go back to reference A. Homami, F. Ghazi, MicroRNAs as biomarkers associated with bladder cancer. Med. J. Islam Repub. Iran. 30, 475 (2016)PubMedPubMedCentral A. Homami, F. Ghazi, MicroRNAs as biomarkers associated with bladder cancer. Med. J. Islam Repub. Iran. 30, 475 (2016)PubMedPubMedCentral

go back to reference H. Wang, J. Wang, Y. Zuo, M. Ding, R. Yan, D. Yang, C. Ke, Expression and prognostic significance of a new tumor metastasis suppressor gene LASS2 in human bladder carcinoma. Med. Oncol. 29, 1921–1927 (2012)PubMed H. Wang, J. Wang, Y. Zuo, M. Ding, R. Yan, D. Yang, C. Ke, Expression and prognostic significance of a new tumor metastasis suppressor gene LASS2 in human bladder carcinoma. Med. Oncol. 29, 1921–1927 (2012)PubMed

go back to reference L. Huang, T. Luan, Y. Chen, X. Bao, Y. Huang, S. Fu, H. Wang, J. Wang, LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial dynamics in bladder cancer cells. J. Cancer 9, 1017–1024 (2018)PubMedPubMedCentral L. Huang, T. Luan, Y. Chen, X. Bao, Y. Huang, S. Fu, H. Wang, J. Wang, LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial dynamics in bladder cancer cells. J. Cancer 9, 1017–1024 (2018)PubMedPubMedCentral

go back to reference D. Witten, R. Tibshirani, S.G. Gu, A. Fire, W.O. Lui, Ultra-high throughput sequencing-based small RNA discovery and discrete statistical biomarker analysis in a collection of cervical tumours and matched controls. BMC Biol. 8, 58 (2010)PubMedPubMedCentral D. Witten, R. Tibshirani, S.G. Gu, A. Fire, W.O. Lui, Ultra-high throughput sequencing-based small RNA discovery and discrete statistical biomarker analysis in a collection of cervical tumours and matched controls. BMC Biol. 8, 58 (2010)PubMedPubMedCentral

go back to reference S. Fu, T. Luan, C. Jiang, Y. Huang, N. Li, H. Wang, J. Wang, MiR-3622a promotes proliferation and invasion of bladder cancer cells by downregulating LASS2. Gene 701, 23–31 (2019) S. Fu, T. Luan, C. Jiang, Y. Huang, N. Li, H. Wang, J. Wang, MiR-3622a promotes proliferation and invasion of bladder cancer cells by downregulating LASS2. Gene 701, 23–31 (2019)

go back to reference T. Luan, R. Zou, L. Huang, N. Li, S. Fu, Y. Huang, H. Wang, J. Wang, Hsa-miR-3658 promotes cell proliferation, migration and invasion by effecting LASS2 in bladder cancer. Clin. Lab. 64, 515–525 (2018)PubMed T. Luan, R. Zou, L. Huang, N. Li, S. Fu, Y. Huang, H. Wang, J. Wang, Hsa-miR-3658 promotes cell proliferation, migration and invasion by effecting LASS2 in bladder cancer. Clin. Lab. 64, 515–525 (2018)PubMed

go back to reference J. Liu, H. Wang, Y. Wang, Z. Li, Y. Pan, Q. Liu, M. Yang, J. Wang, Repression of the mir-93-enhanced sensitivity of bladder carcinoma to chemotherapy involves the regulation of LASS2. Onco. Targets Ther. 9, 1813–1822 (2016) J. Liu, H. Wang, Y. Wang, Z. Li, Y. Pan, Q. Liu, M. Yang, J. Wang, Repression of the mir-93-enhanced sensitivity of bladder carcinoma to chemotherapy involves the regulation of LASS2. Onco. Targets Ther. 9, 1813–1822 (2016)

go back to reference S. Xiao, Y. Chen, T. Luan, Y. Huang, S. Fu, Y. Zuo, H. Wang, J. Wang, MicroRNA-20a targeting LASS2 promotes the proliferation, invasiveness and migration of bladder cancer. Clin. Lab. 67 (2021) S. Xiao, Y. Chen, T. Luan, Y. Huang, S. Fu, Y. Zuo, H. Wang, J. Wang, MicroRNA-20a targeting LASS2 promotes the proliferation, invasiveness and migration of bladder cancer. Clin. Lab. 67 (2021)

go back to reference J. Mesicek, H. Lee, T. Feldman, X. Jiang, A. Skobeleva, E.V. Berdyshev, A. Haimovitz-Friedman, Z. Fuks, R. Kolesnick, Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells. Cell. Signal. 22, 1300–1307 (2010)PubMedPubMedCentral J. Mesicek, H. Lee, T. Feldman, X. Jiang, A. Skobeleva, E.V. Berdyshev, A. Haimovitz-Friedman, Z. Fuks, R. Kolesnick, Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells. Cell. Signal. 22, 1300–1307 (2010)PubMedPubMedCentral

go back to reference N. Sheng, Y.Y. Wang, Y. Xie, S.H. Chen, J. Lu, Z.F. Zhang, M.Q. Li, Q. Shan, D.M. Wu, G.H. Zheng, Y.L. Zheng, S.H. Fan, High expression of LASS2 is associated with unfavorable prognosis in patients with ovarian cancer. J. Cell. Physiol. 234, 13001–13013 (2019)PubMed N. Sheng, Y.Y. Wang, Y. Xie, S.H. Chen, J. Lu, Z.F. Zhang, M.Q. Li, Q. Shan, D.M. Wu, G.H. Zheng, Y.L. Zheng, S.H. Fan, High expression of LASS2 is associated with unfavorable prognosis in patients with ovarian cancer. J. Cell. Physiol. 234, 13001–13013 (2019)PubMed

go back to reference X. Zhang, W. Sakamoto, D. Canals, M. Ishibashi, M. Matsuda, K. Nishida, M. Toyoshima, S. Shigeta, M. Taniguchi, C.E. Senkal, T. Okazaki, N. Yaegashi, Y.A. Hannun, T. Nabe, K. Kitatani, Ceramide synthase 2-C24:1-ceramide axis limits the metastatic potential of ovarian cancer cells. FASEB J. 35, e21287 (2021)PubMed X. Zhang, W. Sakamoto, D. Canals, M. Ishibashi, M. Matsuda, K. Nishida, M. Toyoshima, S. Shigeta, M. Taniguchi, C.E. Senkal, T. Okazaki, N. Yaegashi, Y.A. Hannun, T. Nabe, K. Kitatani, Ceramide synthase 2-C_24:1-ceramide axis limits the metastatic potential of ovarian cancer cells. FASEB J. 35, e21287 (2021)PubMed

go back to reference Y. Zhang, H. Wang, T. Chen, H. Wang, X. Liang, Y. Zhang, J. Duan, S. Qian, K. Qiao, L. Zhang, Y. Liu, J. Wang, C24-Ceramide drives gallbladder cancer progression through directly targeting phosphatidylinositol 5-phosphate 4-kinase type-2 gamma to facilitate mammalian target of rapamycin signaling activation. Hepatology 73, 692–712 (2021)PubMed Y. Zhang, H. Wang, T. Chen, H. Wang, X. Liang, Y. Zhang, J. Duan, S. Qian, K. Qiao, L. Zhang, Y. Liu, J. Wang, C₂₄-Ceramide drives gallbladder cancer progression through directly targeting phosphatidylinositol 5-phosphate 4-kinase type-2 gamma to facilitate mammalian target of rapamycin signaling activation. Hepatology 73, 692–712 (2021)PubMed

go back to reference W.K. Lee, M. Maaß, A. Quach, N. Poscic, H. Prangley, E.C. Pallott, J.L. Kim, J.S. Pierce, B. Ogretmen, A.H. Futerman, F. Thévenod, Dependence of ABCB1 transporter expression and function on distinct sphingolipids generated by ceramide synthases-2 and – 6 in chemoresistant renal cancer. J. Biol. Chem. 298, 101492 (2021)PubMedPubMedCentral W.K. Lee, M. Maaß, A. Quach, N. Poscic, H. Prangley, E.C. Pallott, J.L. Kim, J.S. Pierce, B. Ogretmen, A.H. Futerman, F. Thévenod, Dependence of ABCB1 transporter expression and function on distinct sphingolipids generated by ceramide synthases-2 and – 6 in chemoresistant renal cancer. J. Biol. Chem. 298, 101492 (2021)PubMedPubMedCentral

go back to reference J.J.G. Marin, L. Perez-Silva, R.I.R. Macias, M. Asensio, A. Peleteiro-Vigil, A. Sanchez-Martin, C. Cives-Losada, P. Sanchon-Sanchez, B. Sanchez, E. De Blas, O. Herraez, E. Briz, Lozano, Molecular bases of mechanisms accounting for drug resistance in gastric adenocarcinoma. Cancers 12, 2116 (2020)PubMedPubMedCentral J.J.G. Marin, L. Perez-Silva, R.I.R. Macias, M. Asensio, A. Peleteiro-Vigil, A. Sanchez-Martin, C. Cives-Losada, P. Sanchon-Sanchez, B. Sanchez, E. De Blas, O. Herraez, E. Briz, Lozano, Molecular bases of mechanisms accounting for drug resistance in gastric adenocarcinoma. Cancers 12, 2116 (2020)PubMedPubMedCentral

go back to reference N. Tang, J. Jin, Y. Deng, R.H. Ke, Q.J. Shen, S.H. Fan, W.X. Qin, LASS2 interacts with V-ATPase and inhibits cell growth of hepatocellular carcinoma. Sheng Li Xue Bao 62, 196–202 (2010)PubMed N. Tang, J. Jin, Y. Deng, R.H. Ke, Q.J. Shen, S.H. Fan, W.X. Qin, LASS2 interacts with V-ATPase and inhibits cell growth of hepatocellular carcinoma. Sheng Li Xue Bao 62, 196–202 (2010)PubMed

go back to reference Y. Wang, S. Li, L. Weng, H. Du, J. Wang, X. Xu, LASS2 overexpression enhances early apoptosis of lung cancer cells through the caspasedependent pathway. Oncol. Rep. 48, 220 (2022)PubMed Y. Wang, S. Li, L. Weng, H. Du, J. Wang, X. Xu, LASS2 overexpression enhances early apoptosis of lung cancer cells through the caspasedependent pathway. Oncol. Rep. 48, 220 (2022)PubMed

go back to reference D. Hartmann, J. Lucks, S. Fuchs, S. Schiffmann, Y. Schreiber, N. Ferreirós, J. Merkens, R. Marschalek, G. Geisslinger, S. Grösch, Long chain ceramides and very long chain ceramides have opposite effects on human breast and colon cancer cell growth. Int. J. Biochem. Cell. Biol. 44, 620–628 (2012)PubMed D. Hartmann, J. Lucks, S. Fuchs, S. Schiffmann, Y. Schreiber, N. Ferreirós, J. Merkens, R. Marschalek, G. Geisslinger, S. Grösch, Long chain ceramides and very long chain ceramides have opposite effects on human breast and colon cancer cell growth. Int. J. Biochem. Cell. Biol. 44, 620–628 (2012)PubMed

go back to reference J. Jin, T.D. Mullen, Q. Hou, J. Bielawski, A. Bielawska, X. Zhang, L.M. Obeid, Y.A. Hannun, Y.T. Hsu, AMPK inhibitor compound C stimulates ceramide production and promotes bax redistribution and apoptosis in MCF7 breast carcinoma cells. J. Lipid Res. 50, 2389–2397 (2009)PubMedPubMedCentral J. Jin, T.D. Mullen, Q. Hou, J. Bielawski, A. Bielawska, X. Zhang, L.M. Obeid, Y.A. Hannun, Y.T. Hsu, AMPK inhibitor compound C stimulates ceramide production and promotes bax redistribution and apoptosis in MCF7 breast carcinoma cells. J. Lipid Res. 50, 2389–2397 (2009)PubMedPubMedCentral

go back to reference M. Rabionet, A.C. van der Spoel, C.C. Chuang, B. von Tümpling-Radosta, M. Litjens, D. Bouwmeester, C.C. Hellbusch, C. Körner, H. Wiegandt, K. Gorgas, F.M. Platt, H.J. Gröne, R. Sandhoff, Male germ cells require polyenoic sphingolipids with complex glycosylation for completion of meiosis: a link to ceramide synthase-3. J. Biol. Chem. 283, 13357–13369 (2008)PubMedPubMedCentral M. Rabionet, A.C. van der Spoel, C.C. Chuang, B. von Tümpling-Radosta, M. Litjens, D. Bouwmeester, C.C. Hellbusch, C. Körner, H. Wiegandt, K. Gorgas, F.M. Platt, H.J. Gröne, R. Sandhoff, Male germ cells require polyenoic sphingolipids with complex glycosylation for completion of meiosis: a link to ceramide synthase-3. J. Biol. Chem. 283, 13357–13369 (2008)PubMedPubMedCentral

go back to reference Y. Mizutani, A. Kihara, H. Chiba, H. Tojo, Y. Igarashi, 2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis for the preference of FA chain length. J. Lipid Res. 49, 2356–2364 (2008)PubMed Y. Mizutani, A. Kihara, H. Chiba, H. Tojo, Y. Igarashi, 2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis for the preference of FA chain length. J. Lipid Res. 49, 2356–2364 (2008)PubMed

go back to reference K. Gustafsson, B. Sander, J. Bielawski, Y.A. Hannun, J. Flygare, Potentiation of cannabinoid-induced cytotoxicity in mantle cell lymphoma through modulation of ceramide metabolism. Mol. Cancer Res. 7, 1086–1098 (2009)PubMedPubMedCentral K. Gustafsson, B. Sander, J. Bielawski, Y.A. Hannun, J. Flygare, Potentiation of cannabinoid-induced cytotoxicity in mantle cell lymphoma through modulation of ceramide metabolism. Mol. Cancer Res. 7, 1086–1098 (2009)PubMedPubMedCentral

go back to reference A.H. Janneh, B. Ogretmen, Targeting sphingolipid metabolism as a therapeutic strategy in cancer treatment. Cancers 14, 2183 (2022)PubMedPubMedCentral A.H. Janneh, B. Ogretmen, Targeting sphingolipid metabolism as a therapeutic strategy in cancer treatment. Cancers 14, 2183 (2022)PubMedPubMedCentral

go back to reference D. Verlekar, S.J. Wei, H. Cho, S. Yang, M.H. Kang, Ceramide synthase-6 confers resistance to chemotherapy by binding to CD95/Fas in T-cell acute lymphoblastic leukemia. Cell. Death Dis. 9, 925 (2018)PubMedPubMedCentral D. Verlekar, S.J. Wei, H. Cho, S. Yang, M.H. Kang, Ceramide synthase-6 confers resistance to chemotherapy by binding to CD95/Fas in T-cell acute lymphoblastic leukemia. Cell. Death Dis. 9, 925 (2018)PubMedPubMedCentral

go back to reference E.L. Laviad, L. Albee, I. Pankova-Kholmyansky, S. Epstein, H. Park, A.H. Merrill Jr., A.H. Futerman, Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate. J. Biol. Chem. 283, 5677–5684 (2008)PubMed E.L. Laviad, L. Albee, I. Pankova-Kholmyansky, S. Epstein, H. Park, A.H. Merrill Jr., A.H. Futerman, Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate. J. Biol. Chem. 283, 5677–5684 (2008)PubMed

go back to reference J.W. Chen, X. Li, D. Ma, T. Liu, P. Tian, C. Wu, Ceramide synthase-4 orchestrates the cell proliferation and tumor growth of liver cancer in vitro and in vivo through the nuclear factor-κB signaling pathway. Oncol. Lett. 14, 1477–1483 (2017)PubMedPubMedCentral J.W. Chen, X. Li, D. Ma, T. Liu, P. Tian, C. Wu, Ceramide synthase-4 orchestrates the cell proliferation and tumor growth of liver cancer in vitro and in vivo through the nuclear factor-κB signaling pathway. Oncol. Lett. 14, 1477–1483 (2017)PubMedPubMedCentral

go back to reference M.S. Wegner, L. Gruber, N. Schömel, S. Trautmann, S. Brachtendorf, D. Fuhrmann, Y. Schreiber, C. Olesch, B. Brüne, G. Geisslinger, S. Grösch, GPER1 influences cellular homeostasis and cytostatic drug resistance via influencing long chain ceramide synthesis in breast cancer cells. Int. J. Biochem. Cell. Biol. 112, 95–106 (2019)PubMed M.S. Wegner, L. Gruber, N. Schömel, S. Trautmann, S. Brachtendorf, D. Fuhrmann, Y. Schreiber, C. Olesch, B. Brüne, G. Geisslinger, S. Grösch, GPER1 influences cellular homeostasis and cytostatic drug resistance via influencing long chain ceramide synthesis in breast cancer cells. Int. J. Biochem. Cell. Biol. 112, 95–106 (2019)PubMed

go back to reference A.A. de Jesus, Y. Hou, S. Brooks, L. Malle, A. Biancotto, Y. Huang, K.R. Calvo, B. Marrero, S. Moir, A.J. Oler, Z. Deng, G.A. Montealegre Sanchez, A. Ahmed, E. Allenspach, B. Arabshahi, E. Behrens, S. Benseler, L. Bezrodnik, S. Bout-Tabaku, A.C. Brescia, D. Brown, J.M. Burnham, M.S. Caldirola, R. Carrasco, A.Y. Chan, R. Cimaz, P. Dancey, J. Dare, M. DeGuzman, V. Dimitriades, I. Ferguson, P. Ferguson, L. Finn, M. Gattorno, A.A. Grom, E.P. Hanson, P.J. Hashkes, C.M. Hedrich, R. Herzog, G. Horneff, R. Jerath, E. Kessler, H. Kim, D.J. Kingsbury, R.M. Laxer, P.Y. Lee, M.A. Lee-Kirsch, L. Lewandowski, S. Li, V. Lilleby, V. Mammadova, L.N. Moorthy, G. Nasrullayeva, K.M. O’Neil, K. Onel, S. Ozen, N. Pan, P. Pillet, D.G. Piotto, M.G. Punaro, A. Reiff, A. Reinhardt, L.G. Rider, R. Rivas-Chacon, T. Ronis, A. Rösen-Wolff, J. Roth, N.M. Ruth, M. Rygg, H. Schmeling, G. Schulert, C. Scott, G. Seminario, A. Shulman, V. Sivaraman, M.B. Son, Y. Stepanovskiy, E. Stringer, S. Taber, M.T. Terreri, C. Tifft, T. Torgerson, L. Tosi, A. Van Royen-Kerkhof, T. Wampler Muskardin, S.W. Canna, R. Goldbach-Mansky, Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases. J. Clin. Invest. 130, 1669–1682 (2020) A.A. de Jesus, Y. Hou, S. Brooks, L. Malle, A. Biancotto, Y. Huang, K.R. Calvo, B. Marrero, S. Moir, A.J. Oler, Z. Deng, G.A. Montealegre Sanchez, A. Ahmed, E. Allenspach, B. Arabshahi, E. Behrens, S. Benseler, L. Bezrodnik, S. Bout-Tabaku, A.C. Brescia, D. Brown, J.M. Burnham, M.S. Caldirola, R. Carrasco, A.Y. Chan, R. Cimaz, P. Dancey, J. Dare, M. DeGuzman, V. Dimitriades, I. Ferguson, P. Ferguson, L. Finn, M. Gattorno, A.A. Grom, E.P. Hanson, P.J. Hashkes, C.M. Hedrich, R. Herzog, G. Horneff, R. Jerath, E. Kessler, H. Kim, D.J. Kingsbury, R.M. Laxer, P.Y. Lee, M.A. Lee-Kirsch, L. Lewandowski, S. Li, V. Lilleby, V. Mammadova, L.N. Moorthy, G. Nasrullayeva, K.M. O’Neil, K. Onel, S. Ozen, N. Pan, P. Pillet, D.G. Piotto, M.G. Punaro, A. Reiff, A. Reinhardt, L.G. Rider, R. Rivas-Chacon, T. Ronis, A. Rösen-Wolff, J. Roth, N.M. Ruth, M. Rygg, H. Schmeling, G. Schulert, C. Scott, G. Seminario, A. Shulman, V. Sivaraman, M.B. Son, Y. Stepanovskiy, E. Stringer, S. Taber, M.T. Terreri, C. Tifft, T. Torgerson, L. Tosi, A. Van Royen-Kerkhof, T. Wampler Muskardin, S.W. Canna, R. Goldbach-Mansky, Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases. J. Clin. Invest. 130, 1669–1682 (2020)

go back to reference F.R. Greten, M. Karin, The IKK/NF-κB activation pathway-a target for prevention and treatment of cancer. Cancer Lett. 206, 193–199 (2004)PubMed F.R. Greten, M. Karin, The IKK/NF-κB activation pathway-a target for prevention and treatment of cancer. Cancer Lett. 206, 193–199 (2004)PubMed

go back to reference T. Kawai, S. Akira, Signaling to NF-κB by toll-like receptors. Trends Mol. Med. 13, 460–469 (2007)PubMed T. Kawai, S. Akira, Signaling to NF-κB by toll-like receptors. Trends Mol. Med. 13, 460–469 (2007)PubMed

go back to reference R. Tidhar, S. Ben-Dor, E. Wang, S. Kelly, A.H. Merrill Jr., A.H. Futerman, Acyl chain specificity of ceramide synthases is determined within a region of 150 residues in the Tram-Lag-CLN8 (TLC) domain. J. Biol. Chem. 287, 3197–3206 (2012)PubMed R. Tidhar, S. Ben-Dor, E. Wang, S. Kelly, A.H. Merrill Jr., A.H. Futerman, Acyl chain specificity of ceramide synthases is determined within a region of 150 residues in the Tram-Lag-CLN8 (TLC) domain. J. Biol. Chem. 287, 3197–3206 (2012)PubMed

go back to reference Z. Xu, J. Zhou, D.M. McCoy, R.K. Mallampalli, LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia. J. Lipid Res. 46, 1229–1238 (2005)PubMed Z. Xu, J. Zhou, D.M. McCoy, R.K. Mallampalli, LASS5 is the predominant ceramide synthase isoform involved in de novo sphingolipid synthesis in lung epithelia. J. Lipid Res. 46, 1229–1238 (2005)PubMed

go back to reference I. Becker, L. Wang-Eckhardt, A. Yaghootfam, V. Gieselmann, M. Eckhardt, Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2, Histochem. Cell. Biol. 129, 233–241 (2008) I. Becker, L. Wang-Eckhardt, A. Yaghootfam, V. Gieselmann, M. Eckhardt, Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2, Histochem. Cell. Biol. 129, 233–241 (2008)

go back to reference S.J. Zhang, Y. Wang, L. Yuan, C. Hu, Z. Xu, X. Cheng, High expression of ceramide synthase 5 predicts a poor prognosis in gastric cancer. Transl. Cancer Res 11, 3209–3221 (2022)PubMedPubMedCentral S.J. Zhang, Y. Wang, L. Yuan, C. Hu, Z. Xu, X. Cheng, High expression of ceramide synthase 5 predicts a poor prognosis in gastric cancer. Transl. Cancer Res 11, 3209–3221 (2022)PubMedPubMedCentral

go back to reference G. Zhou, R. Myers, Y. Li, Y. Chen, X. Shen, J. Fenyk-Melody, M. Wu, J. Ventre, T. Doebber, N. Fujii, N. Musi, M.F. Hirshman, L.J. Goodyear, D.E. Moller, Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167–1174 (2001)PubMedPubMedCentral G. Zhou, R. Myers, Y. Li, Y. Chen, X. Shen, J. Fenyk-Melody, M. Wu, J. Ventre, T. Doebber, N. Fujii, N. Musi, M.F. Hirshman, L.J. Goodyear, D.E. Moller, Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167–1174 (2001)PubMedPubMedCentral

go back to reference B.O. Schroeder, F. Bäckhed, Signals from the gut microbiota to distant organs in physiology and disease. Nat. Med. 22, 1079–1089 (2016)PubMed B.O. Schroeder, F. Bäckhed, Signals from the gut microbiota to distant organs in physiology and disease. Nat. Med. 22, 1079–1089 (2016)PubMed

go back to reference O. Boulard, S. Kirchberger, D.J. Royston, K.J. Maloy, F.M. Powrie, Identification of a genetic locus controlling bacteria-driven colitis and associated cancer through effects on innate inflammation. J. Exp. Med. 209, 1309–1324 (2012)PubMedPubMedCentral O. Boulard, S. Kirchberger, D.J. Royston, K.J. Maloy, F.M. Powrie, Identification of a genetic locus controlling bacteria-driven colitis and associated cancer through effects on innate inflammation. J. Exp. Med. 209, 1309–1324 (2012)PubMedPubMedCentral

go back to reference Y. Zhu, L. Gu, X. Lin, J. Zhang, Y. Tang, X. Zhou, B. Lu, X. Lin, C. Liu, E.V. Prochownik, Y. Li, Ceramide-mediated gut dysbiosis enhances cholesterol esterification and promotes colorectal tumorigenesis in mice. JCI. Insight 7, 150607 (2022) Y. Zhu, L. Gu, X. Lin, J. Zhang, Y. Tang, X. Zhou, B. Lu, X. Lin, C. Liu, E.V. Prochownik, Y. Li, Ceramide-mediated gut dysbiosis enhances cholesterol esterification and promotes colorectal tumorigenesis in mice. JCI. Insight 7, 150607 (2022)

go back to reference R. Mojakgomo, Z. Mbita, Z. Dlamini, Linking the ceramide synthases (CerSs) 4 and 5 with apoptosis, endometrial and colon cancers. Exp. Mol. Pathol. 98, 585–592 (2015)PubMed R. Mojakgomo, Z. Mbita, Z. Dlamini, Linking the ceramide synthases (CerSs) 4 and 5 with apoptosis, endometrial and colon cancers. Exp. Mol. Pathol. 98, 585–592 (2015)PubMed

go back to reference S. Fitzgerald, K.M. Sheehan, V. Espina, A. O’Grady, R. Cummins, D. Kenny, L. Liotta, R. O’Kennedy, E.W. Kay, G.S. Kijanka, High CerS5 expression levels associate with reduced patient survival and transition from apoptotic to autophagy signalling pathways in colorectal cancer. J. Pathol. Clin. Res. 1, 54–65 (2015)PubMed S. Fitzgerald, K.M. Sheehan, V. Espina, A. O’Grady, R. Cummins, D. Kenny, L. Liotta, R. O’Kennedy, E.W. Kay, G.S. Kijanka, High CerS5 expression levels associate with reduced patient survival and transition from apoptotic to autophagy signalling pathways in colorectal cancer. J. Pathol. Clin. Res. 1, 54–65 (2015)PubMed

go back to reference S. Brachtendorf, R.A. Wanger, K. Birod, D. Thomas, S. Trautmann, M.S. Wegner, D.C. Fuhrmann, B. Brüne, G. Geisslinger, S. Grösch, Chemosensitivity of human colon cancer cells is influenced by a p53-dependent enhancement of ceramide synthase 5 and induction of autophagy. Biochim. Biophys. Acta Mol. Cell. Biol. Lipids 1863, 1214–1227 (2018)PubMed S. Brachtendorf, R.A. Wanger, K. Birod, D. Thomas, S. Trautmann, M.S. Wegner, D.C. Fuhrmann, B. Brüne, G. Geisslinger, S. Grösch, Chemosensitivity of human colon cancer cells is influenced by a p53-dependent enhancement of ceramide synthase 5 and induction of autophagy. Biochim. Biophys. Acta Mol. Cell. Biol. Lipids 1863, 1214–1227 (2018)PubMed

go back to reference J. Lee, H. Savage, S. Maegawa, R. Ballarò, S. Pareek, B.S. Guerrouahen, V. Gopalakrishnan, K. Schadler, Exercise promotes pro-apoptotic ceramide signaling in a mouse melanoma model. Cancers 14, 4306 (2022)PubMedPubMedCentral J. Lee, H. Savage, S. Maegawa, R. Ballarò, S. Pareek, B.S. Guerrouahen, V. Gopalakrishnan, K. Schadler, Exercise promotes pro-apoptotic ceramide signaling in a mouse melanoma model. Cancers 14, 4306 (2022)PubMedPubMedCentral

go back to reference T.S. Tirodkar, P. Lu, A. Bai, M.J. Scheffel, S. Gencer, E. Garrett-Mayer, A. Bielawska, B. Ogretmen, C. Voelkel-Johnson, Expression of ceramide synthase 6 transcriptionally acid ceramidase in a c-Jun N-terminal kinase (JNK)-dependent manner. J. Biol. Chem. 290, 13157–13167 (2015)PubMedPubMedCentral T.S. Tirodkar, P. Lu, A. Bai, M.J. Scheffel, S. Gencer, E. Garrett-Mayer, A. Bielawska, B. Ogretmen, C. Voelkel-Johnson, Expression of ceramide synthase 6 transcriptionally acid ceramidase in a c-Jun N-terminal kinase (JNK)-dependent manner. J. Biol. Chem. 290, 13157–13167 (2015)PubMedPubMedCentral

go back to reference S.J. Li, Y. Wu, Y. Ding, M. Yu, Z. Ai, CerS6 regulates cisplatin resistance in oral squamous cell carcinoma by altering mitochondrial fission and autophagy. J. Cell. Physiol. 233, 9416–9425 (2018)PubMed S.J. Li, Y. Wu, Y. Ding, M. Yu, Z. Ai, CerS6 regulates cisplatin resistance in oral squamous cell carcinoma by altering mitochondrial fission and autophagy. J. Cell. Physiol. 233, 9416–9425 (2018)PubMed

go back to reference R. Bassan, J.P. Bourquin, D.J. DeAngelo, S. Chiaretti, New approaches to the management of adult acute lymphoblastic leukemia. J. Clin. Oncol. 36, 3504–3519 (2018) R. Bassan, J.P. Bourquin, D.J. DeAngelo, S. Chiaretti, New approaches to the management of adult acute lymphoblastic leukemia. J. Clin. Oncol. 36, 3504–3519 (2018)

go back to reference J.H. Song, K. Kandasamy, A.S. Kraft, ABT-737 induces expression of the death receptor 5 and sensitizes human cancer cells to TRAIL-induced apoptosis. J. Biol. Chem. 283, 25003–25013 (2008)PubMedPubMedCentral J.H. Song, K. Kandasamy, A.S. Kraft, ABT-737 induces expression of the death receptor 5 and sensitizes human cancer cells to TRAIL-induced apoptosis. J. Biol. Chem. 283, 25003–25013 (2008)PubMedPubMedCentral

go back to reference L.E. Davis, S.C. Shalin, A.J. Tackett, Current state of melanoma diagnosis and treatment. Cancer Biol. Ther. 20, 1366–1379 (2019)PubMedPubMedCentral L.E. Davis, S.C. Shalin, A.J. Tackett, Current state of melanoma diagnosis and treatment. Cancer Biol. Ther. 20, 1366–1379 (2019)PubMedPubMedCentral

go back to reference Y.Y. Tang, K. Cao, Q. Wang, J. Chen, R. Liu, S. Wang, J. Zhou, H. Xie, Silencing of CerS6 increases the invasion and glycolysis of melanoma WM35, WM451 and SK28 cell lines via increased GLUT1-induced downregulation of WNT5A. Oncol. Rep. 35, 2907–2915 (2016)PubMed Y.Y. Tang, K. Cao, Q. Wang, J. Chen, R. Liu, S. Wang, J. Zhou, H. Xie, Silencing of CerS6 increases the invasion and glycolysis of melanoma WM35, WM451 and SK28 cell lines via increased GLUT1-induced downregulation of WNT5A. Oncol. Rep. 35, 2907–2915 (2016)PubMed

go back to reference M.H. Kim, J.W. Park, E.J. Lee, S. Kim, S.H. Shin, J.H. Ahn, Y. Jung, I. Park, W.J. Park, C16-ceramide and sphingosine 1-phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation. Oncol. Rep. 40, 2977–2987 (2018)PubMed M.H. Kim, J.W. Park, E.J. Lee, S. Kim, S.H. Shin, J.H. Ahn, Y. Jung, I. Park, W.J. Park, C16-ceramide and sphingosine 1-phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation. Oncol. Rep. 40, 2977–2987 (2018)PubMed

go back to reference D.L. Holliday, V. Speirs, Choosing the right cell line for breast cancer research. Breast Cancer Res 13, 215 (2011)PubMedPubMedCentral D.L. Holliday, V. Speirs, Choosing the right cell line for breast cancer research. Breast Cancer Res 13, 215 (2011)PubMedPubMedCentral

go back to reference A. Prat, J.S. Parker, O. Karginova, C. Fan, C. Livasy, J.I. Herschkowitz, X. He, C.M. Perou, Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 12, R68 (2010)PubMedPubMedCentral A. Prat, J.S. Parker, O. Karginova, C. Fan, C. Livasy, J.I. Herschkowitz, X. He, C.M. Perou, Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 12, R68 (2010)PubMedPubMedCentral

go back to reference E. Santos, Current approaches to gastric cancer in Peru and Mexico. Transl Gastroenterol. Hepatol. 26, 55 (2017) E. Santos, Current approaches to gastric cancer in Peru and Mexico. Transl Gastroenterol. Hepatol. 26, 55 (2017)

go back to reference Y.H. Uen, C.L. Fang, C.C. Lin, Y.C. Hseu, S.T. Hung, D.P. Sun, K.Y. Lin, Ceramide synthase 6 predicts the prognosis of human gastric cancer: it functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway. Mol. Carcinog. 57, 1675–1689 (2018)PubMed Y.H. Uen, C.L. Fang, C.C. Lin, Y.C. Hseu, S.T. Hung, D.P. Sun, K.Y. Lin, Ceramide synthase 6 predicts the prognosis of human gastric cancer: it functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway. Mol. Carcinog. 57, 1675–1689 (2018)PubMed

go back to reference G. Reiterer, A. Yen, Inhibition of the Janus kinase family increases extracellular signal-regulated kinase 1/2 phosphorylation and causes endoreduplication. Cancer Res. 66, 9083–9089 (2006)PubMed G. Reiterer, A. Yen, Inhibition of the Janus kinase family increases extracellular signal-regulated kinase 1/2 phosphorylation and causes endoreduplication. Cancer Res. 66, 9083–9089 (2006)PubMed

go back to reference D. Separovic, P. Breen, N. Joseph, J. Bielawski, J.S. Pierce, E.V.A.N. Buren, T.I. Gudz, Ceramide synthase 6 knockdown suppresses apoptosis after photodynamic therapy in human head and neck squamous carcinoma cells. Anticancer Res. 32, 753–760 (2012)PubMed D. Separovic, P. Breen, N. Joseph, J. Bielawski, J.S. Pierce, E.V.A.N. Buren, T.I. Gudz, Ceramide synthase 6 knockdown suppresses apoptosis after photodynamic therapy in human head and neck squamous carcinoma cells. Anticancer Res. 32, 753–760 (2012)PubMed

go back to reference Y. Shi, C. Zhou, H. Lu, X. Cui, J. Li, S. Jiang, H. Zhang, R. Zhang, Ceramide synthase 6 predicts poor prognosis and activates the AKT/mTOR/4EBP1 pathway in high-grade serous ovarian cancer. Am. J. Transl Res. 12, 5924–5939 (2020)PubMedPubMedCentral Y. Shi, C. Zhou, H. Lu, X. Cui, J. Li, S. Jiang, H. Zhang, R. Zhang, Ceramide synthase 6 predicts poor prognosis and activates the AKT/mTOR/4EBP1 pathway in high-grade serous ovarian cancer. Am. J. Transl Res. 12, 5924–5939 (2020)PubMedPubMedCentral

go back to reference S. Wullschleger, R. Loewith, M.N. Hall, TOR signaling in growth and metabolism. Cell 124, 471–484 (2006)PubMed S. Wullschleger, R. Loewith, M.N. Hall, TOR signaling in growth and metabolism. Cell 124, 471–484 (2006)PubMed

go back to reference V. Malyla, K.R. Paudel, S.D. Shukla, C. Donovan, R. Wadhwa, S. Pickles, V. Chimankar, P. Sahu, H. Bielefeldt-Ohmann, M. Bebawy, P.M. Hansbro, K. Dua, Recent advances in experimental animal models of lung cancer. Future Med. Chem. 12, 567–570 (2020)PubMed V. Malyla, K.R. Paudel, S.D. Shukla, C. Donovan, R. Wadhwa, S. Pickles, V. Chimankar, P. Sahu, H. Bielefeldt-Ohmann, M. Bebawy, P.M. Hansbro, K. Dua, Recent advances in experimental animal models of lung cancer. Future Med. Chem. 12, 567–570 (2020)PubMed

go back to reference H.X. Shi, A. Niimi, T. Takeuchi, K. Shiogama, Y. Mizutani, T. Kajino, K. Inada, T. Hase, T. Hatta, H. Shibata, T. Fukui, T.F. Chen-Yoshikawa, K. Nagano, T. Murate, Y. Kawamoto, S. Tomida, T. Takahashi, M. Suzuki, CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation. Cancer Sci. 112, 2770–2780 (2021)PubMedPubMedCentral H.X. Shi, A. Niimi, T. Takeuchi, K. Shiogama, Y. Mizutani, T. Kajino, K. Inada, T. Hase, T. Hatta, H. Shibata, T. Fukui, T.F. Chen-Yoshikawa, K. Nagano, T. Murate, Y. Kawamoto, S. Tomida, T. Takahashi, M. Suzuki, CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation. Cancer Sci. 112, 2770–2780 (2021)PubMedPubMedCentral

go back to reference M. Suzuki, K. Cao, S. Kato, N. Mizutani, K. Tanaka, C. Arima, M.C. Tai, N. Nakatani, K. Yanagisawa, T. Takeuchi, H. Shi, Y. Mizutani, A. Niimi, T. Taniguchi, T. Fukui, K. Yokoi, K. Wakahara, Y. Hasegawa, Y. Mizutani, S. Iwaki, S. Fujii, A. Satou, K. Tamiya-Koizumi, T. Murate, M. Kyogashima, S. Tomida, T. Takahashi, CERS6 required for cell migration and metastasis in lung cancer. J. Cell. Mol. Med. 24, 11949–11959 (2020)PubMedPubMedCentral M. Suzuki, K. Cao, S. Kato, N. Mizutani, K. Tanaka, C. Arima, M.C. Tai, N. Nakatani, K. Yanagisawa, T. Takeuchi, H. Shi, Y. Mizutani, A. Niimi, T. Taniguchi, T. Fukui, K. Yokoi, K. Wakahara, Y. Hasegawa, Y. Mizutani, S. Iwaki, S. Fujii, A. Satou, K. Tamiya-Koizumi, T. Murate, M. Kyogashima, S. Tomida, T. Takahashi, CERS6 required for cell migration and metastasis in lung cancer. J. Cell. Mol. Med. 24, 11949–11959 (2020)PubMedPubMedCentral

go back to reference S. Varambally, Q. Cao, R.S. Mani, S. Shankar, X. Wang, B. Ateeq, B. Laxman, X. Cao, X. Jing, K. Ramnarayanan, J.C. Brenner, J. Yu, J.H. Kim, B. Han, P. Tan, C. Kumar-Sinha, R.J. Lonigro, N. Palanisamy, C.A. Maher, A.M. Chinnaiyan, Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322, 1695–1699 (2008)PubMedPubMedCentral S. Varambally, Q. Cao, R.S. Mani, S. Shankar, X. Wang, B. Ateeq, B. Laxman, X. Cao, X. Jing, K. Ramnarayanan, J.C. Brenner, J. Yu, J.H. Kim, B. Han, P. Tan, C. Kumar-Sinha, R.J. Lonigro, N. Palanisamy, C.A. Maher, A.M. Chinnaiyan, Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322, 1695–1699 (2008)PubMedPubMedCentral

go back to reference Y.H. Zhu, J.H. Zheng, Q.Y. Jia, Z.H. Duan, H.F. Yao, J. Yang, Y.W. Sun, S.H. Jiang, D.J. Liu, Y.M. Huo, Immunosuppression, immune escape, and immunotherapy in pancreatic cancer: focused on the tumor microenvironment. Cell. Oncol. (2022) Y.H. Zhu, J.H. Zheng, Q.Y. Jia, Z.H. Duan, H.F. Yao, J. Yang, Y.W. Sun, S.H. Jiang, D.J. Liu, Y.M. Huo, Immunosuppression, immune escape, and immunotherapy in pancreatic cancer: focused on the tumor microenvironment. Cell. Oncol. (2022)

go back to reference D.C. Qi, X. Song, C. Xue, W. Yao, P. Shen, H. Yu, Z. Zhang, AKT1/FOXP3 axis-mediated expression of CerS6 promotes p53 mutant pancreatic tumorigenesis. Cancer Lett. 522, 105–118 (2021)PubMed D.C. Qi, X. Song, C. Xue, W. Yao, P. Shen, H. Yu, Z. Zhang, AKT1/FOXP3 axis-mediated expression of CerS6 promotes p53 mutant pancreatic tumorigenesis. Cancer Lett. 522, 105–118 (2021)PubMed

go back to reference B. Fekry, K.A. Jeffries, A. Esmaeilniakooshkghazi, Z.M. Szulc, K.J. Knagge, D.R. Kirchner, D.A. Horita, S.A. Krupenko, N.I. Krupenko, C16-ceramide is a natural regulatory ligand of p53 in cellular stress response. Nat. Commun. 9, 4149 (2018)PubMedPubMedCentral B. Fekry, K.A. Jeffries, A. Esmaeilniakooshkghazi, Z.M. Szulc, K.J. Knagge, D.R. Kirchner, D.A. Horita, S.A. Krupenko, N.I. Krupenko, C₁₆-ceramide is a natural regulatory ligand of p53 in cellular stress response. Nat. Commun. 9, 4149 (2018)PubMedPubMedCentral

go back to reference L.A. Hoeferlin, B. Fekry, B. Ogretmen, S.A. Krupenko, N.I. Krupenko, Folate stress induces apoptosis via p53-dependent de novo ceramide synthesis and up-regulation of ceramide synthase 6. J. Biol. Chem. 288, 12880–12890 (2013)PubMedPubMedCentral L.A. Hoeferlin, B. Fekry, B. Ogretmen, S.A. Krupenko, N.I. Krupenko, Folate stress induces apoptosis via p53-dependent de novo ceramide synthesis and up-regulation of ceramide synthase 6. J. Biol. Chem. 288, 12880–12890 (2013)PubMedPubMedCentral

go back to reference N. Ron-Harel, A.H. Sharpe, M.C. Haigis, Mitochondrial metabolism in T cell activation and senescence: a mini-review. Gerontology 61, 131–138 (2015)PubMed N. Ron-Harel, A.H. Sharpe, M.C. Haigis, Mitochondrial metabolism in T cell activation and senescence: a mini-review. Gerontology 61, 131–138 (2015)PubMed

go back to reference S. Vaena, P. Chakraborty, H.G. Lee, A.H. Janneh, M.F. Kassir, G. Beeson, Z. Hedley, A. Yalcinkaya, M.H. Sofi, H. Li, M.L. Husby, R.V. Stahelin, X.Z. Yu, S. Mehrotra, B. Ogretmen, Aging-dependent mitochondrial dysfunction mediated by ceramide signaling inhibits antitumor T cell response. Cell. Rep. 35, 109076 (2021)PubMedPubMedCentral S. Vaena, P. Chakraborty, H.G. Lee, A.H. Janneh, M.F. Kassir, G. Beeson, Z. Hedley, A. Yalcinkaya, M.H. Sofi, H. Li, M.L. Husby, R.V. Stahelin, X.Z. Yu, S. Mehrotra, B. Ogretmen, Aging-dependent mitochondrial dysfunction mediated by ceramide signaling inhibits antitumor T cell response. Cell. Rep. 35, 109076 (2021)PubMedPubMedCentral