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Journal of Experimental & Clinical Cancer Research

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01-12-2021 | Breast Cancer | Research

ALG3 contributes to stemness and radioresistance through regulating glycosylation of TGF-β receptor II in breast cancer

Authors: Xiaoqing Sun, Zhenyu He, Ling Guo, Caiqin Wang, Chuyong Lin, Liping Ye, Xiaoqing Wang, Yue Li, Meisongzhu Yang, Sailan Liu, Xin Hua, Wen Wen, Chao Lin, Zhiqing Long, Wenwen Zhang, Han Li, Yunting Jian, Ziyuan Zhu, Xianqiu Wu, Huanxin Lin

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Radiotherapy is a conventional and effective local treatment for breast cancer. However, residual or recurrent tumors appears frequently because of radioresistance. Novel predictive marker and the potential therapeutic targets of breast cancer radioresistance needs to be investigated.

Methods

In this study, we screened all 10 asparagine-linked glycosylation (ALG) members in breast cancer patients’ samples by RT-PCR. Cell viability after irradiation (IR) was determined by CCK-8 assay and flow cytometry. The radiosensitivity of cell lines with different ALG3 expression was determined with the colony formation assay by fitting the multi-target single hit model to the surviving fractions. Cancer stem-like traits were assessed by RT-PCR, Western blot, and flow cytometry. The mechanisms of ALG3 influencing radiosensitivity was detected by Western blot and immunoprecipitation. And the effect of ALG3 on tumor growth after IR was verified in an orthotopic xenograft tumor models. The association of ALG3 with prognosis of breast cancer patients was confirmed by immunohistochemistry.

Results

ALG3 was the most significantly overexpressing gene among ALG family in radioresistant breast cancer tissue. Overexpression of ALG3 predicted poor clinicopathological characteristics and overall survival (OS), and early local recurrence-free survival (LRFS) in breast cancer patients. Upregulating ALG3 enhanced radioresistance and cancer stemness in vitro and in vivo. Conversely, silencing ALG3 increased the radiosensitivity and repressed cancer stemness in vitro, and more importantly inhibition of ALG3 effectively increased the radiosensitivity of breast cancer cells in vivo. Mechanistically, our results further revealed ALG3 promoted radioresistance and cancer stemness by inducing glycosylation of TGF-β receptor II (TGFBR2). Importantly, both attenuation of glycosylation using tunicamycin and inhibition of TGFBR2 using LY2109761 differentially abrogated the stimulatory effect of ALG3 overexpression on cancer stemness and radioresistance. Finally, our findings showed that radiation played an important role in preventing early recurrence in breast cancer patients with low ALG3 levels, but it had limited efficacy in ALG3-overexpressing breast cancer patients.

Conclusion

Our results suggest that ALG3 may serve as a potential radiosensitive marker, and an effective target to decrease radioresistance by regulating glycosylation of TGFBR2 in breast cancer. For patients with low ALG3 levels, radiation remains an effective mainstay therapy to prevent early recurrence in breast cancer.

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Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. https://doi.org/10.3322/caac.21262.CrossRefPubMed

Takahashi M, Hasegawa Y, Gao C, Kuroki Y, Taniguchi N. N-glycans of growth factor receptors: their role in receptor function and disease implications. Clin Sci. 2016;130:1781–92.CrossRef

Ebctcg MGP, Taylor C, Correa C, Cutter D, Duane F, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet (London). 2014;383:2127–35.CrossRef

Sjostrom M, Lundstedt D, Hartman L, Holmberg E, Killander F, Kovacs A, et al. Response to radiotherapy after breast-conserving surgery in different breast Cancer subtypes in the Swedish breast Cancer group 91 radiotherapy randomized clinical trial. J Clin Oncol. 2017;35(28):3222–9. https://doi.org/10.1200/JCO.2017.72.7263.CrossRefPubMed

Krause M, Yaromina A, Eicheler W, Koch U, Baumann M. Cancer stem cells: targets and potential biomarkers for radiotherapy. Clin Cancer Res. 2011;17(23):7224–9. https://doi.org/10.1158/1078-0432.CCR-10-2639.CrossRefPubMed

Grinan-Lison C, Olivares-Urbano MA, Jimenez G, Lopez-Ruiz E, Del Val C, Morata-Tarifa C, et al. miRNAs as radio-response biomarkers for breast cancer stem cells. Mol Oncol. 2020;14(3):556–70. https://doi.org/10.1002/1878-0261.12635.CrossRefPubMedPubMedCentral

Hwang IY, Kwak S, Lee S, Kim H, Lee SE, Kim JH, et al. Psat1-dependent fluctuations in α-Ketoglutarate affect the timing of ESC differentiation. Cell Metab. 2016;24(3):494–501. https://doi.org/10.1016/j.cmet.2016.06.014.CrossRefPubMed

Hagey DW, Topcic D, Kee N, Reynaud F, Bergsland M, Perlmann T, et al. CYCLIN-B1/2 and -D1 act in opposition to coordinate cortical progenitor self-renewal and lineage commitment. Nat Commun. 2020;11(1):2898. https://doi.org/10.1038/s41467-020-16597-8.CrossRefPubMedPubMedCentral

Tanguay DA, Colarusso TP, Pavlovic S, Irigoyen M, Howard RG, Bartek J, et al. Early induction of cyclin D2 expression in phorbol ester-responsive B-1 lymphocytes. J Exp Med. 1999;189(11):1685–90. https://doi.org/10.1084/jem.189.11.1685.CrossRefPubMedPubMedCentral

10.

Zuo ZQ, Chen KG, Yu XY, Zhao G, Shen S, Cao ZT, et al. Promoting tumor penetration of nanoparticles for cancer stem cell therapy by TGF-beta signaling pathway inhibition. Biomaterials. 2016;82:48–59. https://doi.org/10.1016/j.biomaterials.2015.12.014.CrossRefPubMed

11.

Heldin CH, Landstrom M, Moustakas A. Mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition. Curr Opin Cell Biol. 2009;21(2):166–76. https://doi.org/10.1016/j.ceb.2009.01.021.CrossRefPubMed

12.

Zhang Z, Fan Y, Xie F, Zhou H, Jin K, Shao L, et al. Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7. Nat Commun. 2017;8(1):2116. https://doi.org/10.1038/s41467-017-02029-7.CrossRefPubMedPubMedCentral

13.

Zhang J, Ten Dijke P, Wuhrer M, Zhang T. Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer. Protein Cell. 2021;12(2):89-106. https://doi.org/10.1007/s13238-020-00741-7. Epub 2020 Jun 25.

14.

Varki A. Biological roles of glycans. Glycobiology. 2017;27(1):3–49. https://doi.org/10.1093/glycob/cww086.CrossRefPubMed

15.

Barbier V, Erbani J, Fiveash C, Davies JM, Tay J, Tallack MR, et al. Endothelial E-selectin inhibition improves acute myeloid leukaemia therapy by disrupting vascular niche-mediated chemoresistance. Nat Commun. 2020;11(1):2042. https://doi.org/10.1038/s41467-020-15817-5.CrossRefPubMedPubMedCentral

16.

Shen L, Xia M, Deng X, Ke Q, Zhang C, Peng F, et al. A lectin-based glycomic approach identifies FUT8 as a driver of radioresistance in oesophageal squamous cell carcinoma. Cell Oncol. 2020;43(4):695–707. https://doi.org/10.1007/s13402-020-00517-5.CrossRef

17.

Costa AF, Campos D, Reis CA, Gomes C. Targeting glycosylation: a new road for Cancer drug discovery. Trends Cancer. 2020;6(9):757–66. https://doi.org/10.1016/j.trecan.2020.04.002.CrossRefPubMed

18.

Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer. 2015;15(9):540–55. https://doi.org/10.1038/nrc3982.CrossRefPubMed

19.

Hakomori S. Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. Adv Cancer Res. 1989;52:257–331. https://doi.org/10.1016/S0065-230X(08)60215-8.CrossRefPubMed

20.

Meany DL, Chan DW. Aberrant glycosylation associated with enzymes as cancer biomarkers. Clin Proteomics. 2011;8(1):7. https://doi.org/10.1186/1559-0275-8-7.CrossRefPubMedPubMedCentral

21.

Drake RR. Glycosylation and cancer: moving glycomics to the forefront. Adv Cancer Res. 2015;126:1–10. https://doi.org/10.1016/bs.acr.2014.12.002.CrossRefPubMed

22.

Dall'Olio F, Malagolini N, Trinchera M, Chiricolo M. Mechanisms of cancer-associated glycosylation changes. Front Biosci 2012;17: 670–699, 1, doi: https://doi.org/10.2741/3951.

23.

Reily C, Stewart TJ, Renfrow MB, Novak J. Glycosylation in health and disease. Nat Rev Nephrol. 2019;15(6):346–66. https://doi.org/10.1038/s41581-019-0129-4.CrossRefPubMedPubMedCentral

24.

Cheng C, Ru P, Geng F, Liu J, Yoo JY, Wu X, et al. Glucose-mediated N-glycosylation of SCAP is essential for SREBP-1 activation and tumor growth. Cancer Cell. 2015;28(5):569–81. https://doi.org/10.1016/j.ccell.2015.09.021.CrossRefPubMedPubMedCentral

25.

Nagae M, Kizuka Y, Mihara E, Kitago Y, Hanashima S, Ito Y, et al. Structure and mechanism of cancer-associated N-acetylglucosaminyltransferase-V. Nat Commun. 2018;9(1):3380. https://doi.org/10.1038/s41467-018-05931-w.CrossRefPubMedPubMedCentral

26.

Kim YW, Park J, Lee HJ, Lee SY, Kim SJ. TGF-beta sensitivity is determined by N-linked glycosylation of the type II TGF-beta receptor. Biochem J. 2012;445(3):403–11. https://doi.org/10.1042/BJ20111923.CrossRefPubMed

27.

Kornfeld R, Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem. 1985;54(1):631–64. https://doi.org/10.1146/annurev.bi.54.070185.003215.CrossRefPubMed

28.

Trempel F, Kajiura H, Ranf S, Grimmer J, Westphal L, Zipfel C, et al. Altered glycosylation of exported proteins, including surface immune receptors, compromises calcium and downstream signaling responses to microbe-associated molecular patterns in Arabidopsis thaliana. BMC Plant Biol. 2016;16(1):31. https://doi.org/10.1186/s12870-016-0718-3.CrossRefPubMedPubMedCentral

29.

Kajiura H, Seki T, Fujiyama K. Arabidopsis thaliana ALG3 mutant synthesizes immature oligosaccharides in the ER and accumulates unique N-glycans. Glycobiology. 2010;20(6):736–51. https://doi.org/10.1093/glycob/cwq028.CrossRefPubMed

30.

Munkley J, Mills IG, Elliott DJ. The role of glycans in the development and progression of prostate cancer. Nat Rev Urol. 2016;13(6):324–33. https://doi.org/10.1038/nrurol.2016.65.CrossRefPubMed

31.

de Leoz ML, Young LJ, An HJ, Kronewitter SR, Kim J, Miyamoto S, et al. High-mannose glycans are elevated during breast cancer progression. Mol Cell Proteomics. 2011;10:M110 002717.CrossRefPubMed

32.

Shi ZZ, Jiang YY, Hao JJ, Zhang Y, Zhang TT, Shang L, et al. Identification of putative target genes for amplification within 11q13.2 and 3q27.1 in esophageal squamous cell carcinoma. Clin Transl Oncol. 2014;16(7):606–15. https://doi.org/10.1007/s12094-013-1124-z.CrossRefPubMed

33.

Choi YW, Bae SM, Kim YW, Lee HN, Kim YW, Park TC, et al. Gene expression profiles in squamous cell cervical carcinoma using array-based comparative genomic hybridization analysis. Int J Gynecol Cancer. 2007;17(3):687–96. https://doi.org/10.1111/j.1525-1438.2007.00834.x.CrossRefPubMed

34.

Liu B, Ma X, Liu Q, Xiao Y, Pan S, Jia L. Aberrant mannosylation profile and FTX/miR-342/ALG3-axis contribute to development of drug resistance in acute myeloid leukemia. Cell Death Dis. 2018;9(6):688. https://doi.org/10.1038/s41419-018-0706-7.CrossRefPubMedPubMedCentral

35.

de Vreede G, Morrison HA, Houser AM, Boileau RM, Andersen D, Colombani J, et al. A Drosophila tumor suppressor gene prevents tonic TNF signaling through receptor N-glycosylation. Dev Cell. 2018;45(5):595–605 e594. https://doi.org/10.1016/j.devcel.2018.05.012.CrossRefPubMedPubMedCentral

36.

Aebi M, Gassenhuber J, Domdey H, te Heesen S. Cloning and characterization of the ALG3 gene of Saccharomyces cerevisiae. Glycobiology. 1996;6(4):439–44. https://doi.org/10.1093/glycob/6.4.439.CrossRefPubMed

37.

Partridge EA, Le Roy C, Di Guglielmo GM, Pawling J, Cheung P, Granovsky M, et al. Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science (New York). 2004;306:120–4.CrossRef

38.

Lei T, Zhang P, Zhang X, Xiao X, Zhang J, Qiu T, et al. Cyclin K regulates prereplicative complex assembly to promote mammalian cell proliferation. Nat Commun. 2018;9(1):1876. https://doi.org/10.1038/s41467-018-04258-w.CrossRefPubMedPubMedCentral

39.

Sinn HP, Helmchen B, Wittekind CH. TNM classification of breast cancer: changes and comments on the 7th edition. Pathologe. 2010;31(5):361–6. https://doi.org/10.1007/s00292-010-1307-0.CrossRefPubMed

40.

Simpson JF, Gray R, Dressler LG, Cobau CD, Falkson CI, Gilchrist KW, et al. Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189. J Clin Oncol. 2000;18(10):2059–69. https://doi.org/10.1200/JCO.2000.18.10.2059.CrossRefPubMed

41.

Zeng Z, Lin H, Zhao X, Liu G, Wang X, Xu R, et al. Overexpression of GOLPH3 promotes proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor. Clin Cancer Res. 2012;18(15):4059–69. https://doi.org/10.1158/1078-0432.CCR-11-3156.CrossRefPubMed

42.

Liu G, Zheng H, Zhang Z, Wu Z, Xiong H, Li J, et al. Overexpression of sphingosine kinase 1 is associated with salivary gland carcinoma progression and might be a novel predictive marker for adjuvant therapy. BMC Cancer. 2010;10(1):495. https://doi.org/10.1186/1471-2407-10-495.CrossRefPubMedPubMedCentral

43.

Wang X, Lin C, Zhao X, Liu A, Zhu J, Li X, et al. Acylglycerol kinase promotes cell proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor. Mol Cancer. 2014;13(1):106. https://doi.org/10.1186/1476-4598-13-106.CrossRefPubMedPubMedCentral

44.

Lee YC, Wang WL, Chang WC, Huang YH, Hong GC, Wang HL, et al. Tribbles homolog 3 involved in radiation response of triple negative breast Cancer cells by regulating Notch1 activation. Cancers. 2019;11(2):127.

45.

Candas D, Lu CL, Fan M, Chuang FY, Sweeney C, Borowsky AD, et al. Mitochondrial MKP1 is a target for therapy-resistant HER2-positive breast cancer cells. Cancer Res. 2014;74(24):7498–509. https://doi.org/10.1158/0008-5472.CAN-14-0844.CrossRefPubMedPubMedCentral

46.

Speers C, Zhao S, Liu M, Bartelink H, Pierce LJ, Feng FY. Development and validation of a novel Radiosensitivity signature in human breast Cancer. Clin Cancer Res. 2015;21(16):3667–77. https://doi.org/10.1158/1078-0432.CCR-14-2898.CrossRefPubMed

47.

Zhong Q, Liu ZH, Lin ZR, Hu ZD, Yuan L, Liu YM, et al. The RARS-MAD1L1 fusion gene induces Cancer stem cell-like properties and therapeutic resistance in nasopharyngeal carcinoma. Clin Cancer Res. 2018;24(3):659–73. https://doi.org/10.1158/1078-0432.CCR-17-0352.CrossRefPubMed

48.

Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, et al. The JAK2/STAT3 signaling pathway is required for growth of CD44(+)CD24(−) stem cell-like breast cancer cells in human tumors. J Clin Invest. 2011;121(7):2723–35. https://doi.org/10.1172/JCI44745.CrossRefPubMedPubMedCentral

49.

Johansson J, Naszai M, Hodder MC, Pickering KA, Miller BW, Ridgway RA, et al. RAL GTPases drive intestinal stem cell function and regeneration through internalization of WNT Signalosomes. Cell Stem Cell. 2019;24(4):592–607 e597. https://doi.org/10.1016/j.stem.2019.02.002.CrossRefPubMedPubMedCentral

50.

Ren D, Dai Y, Yang Q, Zhang X, Guo W, Ye L, et al. Wnt5a induces and maintains prostate cancer cells dormancy in bone. J Exp Med. 2019;216(2):428–49. https://doi.org/10.1084/jem.20180661.CrossRefPubMedPubMedCentral

51.

Chaffer CL, Marjanovic ND, Lee T, Bell G, Kleer CG, Reinhardt F, et al. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell. 2013;154(1):61–74. https://doi.org/10.1016/j.cell.2013.06.005.CrossRefPubMedPubMedCentral

52.

Majumdar A, Curley SA, Wu X, Brown P, Hwang JP, Shetty K, et al. Hepatic stem cells and transforming growth factor β in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2012;9(9):530–8. https://doi.org/10.1038/nrgastro.2012.114.CrossRefPubMedPubMedCentral

53.

Le Belle JE, Orozco NM, Paucar AA, Saxe JP, Mottahedeh J, Pyle AD, et al. Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner. Cell Stem Cell. 2011;8(1):59–71. https://doi.org/10.1016/j.stem.2010.11.028.CrossRefPubMedPubMedCentral

54.

Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer. 2011;11(6):393–410. https://doi.org/10.1038/nrc3064.CrossRefPubMed

55.

Krisko A, Leroy M, Radman M, Meselson M. Extreme anti-oxidant protection against ionizing radiation in bdelloid rotifers. Proc Natl Acad Sci U S A. 2012;109(7):2354–7. https://doi.org/10.1073/pnas.1119762109.CrossRefPubMedPubMedCentral

56.

Henquet M, Lehle L, Schreuder M, Rouwendal G, Molthoff J, Helsper J, et al. Identification of the gene encoding the alpha1,3-mannosyltransferase (ALG3) in Arabidopsis and characterization of downstream n-glycan processing. Plant Cell. 2008;20(6):1652–64. https://doi.org/10.1105/tpc.108.060731.CrossRefPubMedPubMedCentral

57.

Partridge EA. Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science. 2004;306(5693):120–4. https://doi.org/10.1126/science.1102109.CrossRefPubMed

58.

Hasnain SZ, Tauro S, Das I, Tong H, Chen AC, Jeffery PL, et al. IL-10 promotes production of intestinal mucus by suppressing protein misfolding and endoplasmic reticulum stress in goblet cells. Gastroenterology. 2013;144(2):357–68 e359. https://doi.org/10.1053/j.gastro.2012.10.043.CrossRefPubMed

59.

Y L, Y H, W B, L X, Y C, K L, et al. Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer. 2019;11(521):eaax0428.

60.

Yamamoto K, Ichikawa S. Tunicamycin: chemical synthesis and biosynthesis. J Antibiot. 2019;72(12):924–33. https://doi.org/10.1038/s41429-019-0200-1.CrossRef

61.

Zhang M, Kleber S, Rohrich M, Timke C, Han N, Tuettenberg J, et al. Blockade of TGF-beta signaling by the TGFbetaR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Cancer Res. 2011;71(23):7155–67. https://doi.org/10.1158/0008-5472.CAN-11-1212.CrossRefPubMed

62.

Cao L, Kim S, Xiao C, Wang RH, Coumoul X, Wang X, et al. ATM-Chk2-p53 activation prevents tumorigenesis at an expense of organ homeostasis upon Brca1 deficiency. EMBO J. 2006;25(10):2167–77. https://doi.org/10.1038/sj.emboj.7601115.CrossRefPubMedPubMedCentral

63.

Jin H, Rugira T, Ko YS, Park SW, Yun SP, Kim HJ. ESM-1 overexpression is involved in increased tumorigenesis of radiotherapy-resistant breast Cancer cells. Cancers. 2020;12(6). https://doi.org/10.3390/cancers12061363.

64.

Wolfort R, de Benedetti A, Nuthalapaty S, Yu H, Chu QD, Li BD. Up-regulation of TLK1B by eIF4E overexpression predicts cancer recurrence in irradiated patients with breast cancer. Surgery. 2006;140(2):161–9. https://doi.org/10.1016/j.surg.2006.05.001.CrossRefPubMed

65.

Shao Z, Ma X, Zhang Y, Sun Y, Lv W, He K, et al. CPNE1 predicts poor prognosis and promotes tumorigenesis and radioresistance via the AKT singling pathway in triple-negative breast cancer. Mol Carcinog. 2020;59(5):533–44. https://doi.org/10.1002/mc.23177.CrossRefPubMedPubMedCentral

66.

Garvin S, Oda H, Arnesson LG, Lindstrom A, Shabo I. Tumor cell expression of CD163 is associated to postoperative radiotherapy and poor prognosis in patients with breast cancer treated with breast-conserving surgery. J Cancer Res Clin Oncol. 2018;144(7):1253–63. https://doi.org/10.1007/s00432-018-2646-0.CrossRefPubMedPubMedCentral

67.

Leerapun A, Suravarapu SV, Bida JP, Clark RJ, Sanders EL, Mettler TA, et al. The utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: evaluation in a United States referral population. Clin Gastroenterol Hepatol. 2007;5(3):394–402; quiz 267. https://doi.org/10.1016/j.cgh.2006.12.005.CrossRefPubMedPubMedCentral

68.

Auclin E, Andre T, Taieb J, Benetkiewicz M, de Gramont A, Vernerey D. Low-level postoperative carcinoembryonic antigen improves survival outcomes stratification in patients with stage II colon cancer treated with standard adjuvant treatments. Eur J Cancer (Oxford). 2018;97:55–6.CrossRef

69.

Albertsen PC. Prostate cancer screening with prostate-specific antigen: where are we going? Cancer. 2018;124(3):453–5. https://doi.org/10.1002/cncr.31140.CrossRefPubMed

70.

Knezevic J, Pfefferle AD, Petrovic I, Greene SB, Perou CM, Rosen JM. Expression of miR-200c in claudin-low breast cancer alters stem cell functionality, enhances chemosensitivity and reduces metastatic potential. Oncogene. 2015;34(49):5997–6006. https://doi.org/10.1038/onc.2015.48.CrossRefPubMedPubMedCentral

71.

Siveen KS, Uddin S, Mohammad RM. Targeting acute myeloid leukemia stem cell signaling by natural products. Mol Cancer. 2017;16(1):13. https://doi.org/10.1186/s12943-016-0571-x.CrossRefPubMedPubMedCentral

72.

Vitale I, Manic G, De Maria R, Kroemer G, Galluzzi L. DNA Damage in Stem Cells. Mol Cell. 2017;66(3):306–19. https://doi.org/10.1016/j.molcel.2017.04.006.CrossRefPubMed

73.

Semenza GL. Dynamic regulation of stem cell specification and maintenance by hypoxia-inducible factors. Mol Aspects Med. 2016;47–48:15–23.CrossRefPubMed

74.

Yong Y, Zhang C, Gu Z, Du J, Guo Z, Dong X, et al. Polyoxometalate-based Radiosensitization platform for treating hypoxic tumors by attenuating Radioresistance and enhancing radiation response. ACS Nano. 2017;11(7):7164–76. https://doi.org/10.1021/acsnano.7b03037.CrossRefPubMed

75.

Camus-Bouclainville C, Gretillat M, Py R, Gelfi J, Guerin JL, Bertagnoli S. Genome sequence of SG33 strain and recombination between wild-type and vaccine myxoma viruses. Emerg Infect Dis. 2011;17(4):633–8. https://doi.org/10.3201/eid1704.101146.CrossRefPubMedPubMedCentral

76.

Stadlmann J, Taubenschmid J, Wenzel D, Gattinger A, Durnberger G, Dusberger F, et al. Comparative glycoproteomics of stem cells identifies new players in ricin toxicity. Nature. 2017;549(7673):538–42. https://doi.org/10.1038/nature24015.CrossRefPubMedPubMedCentral

77.

Wang YC, Peterson SE, Loring JF. Protein post-translational modifications and regulation of pluripotency in human stem cells. Cell Res. 2014;24(2):143–60. https://doi.org/10.1038/cr.2013.151.CrossRefPubMed

78.

Ferreira IG, Pucci M, Venturi G, Malagolini N, Chiricolo M, Dall'Olio F. Glycosylation as a Main regulator of growth and death factor receptors signaling. Int J Mol Sci. 2018;19(2):580.

79.

Zorzan I, Pellegrini M, Arboit M, Incarnato D, Maldotti M, Forcato M, et al. The transcriptional regulator ZNF398 mediates pluripotency and epithelial character downstream of TGF-beta in human PSCs. Nat Commun. 2020;11(1):2364. https://doi.org/10.1038/s41467-020-16205-9.CrossRefPubMedPubMedCentral

80.

Wang X, Inoue S, Gu J, Miyoshi E, Noda K, Li W, et al. Dysregulation of TGF-beta1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice. Proc Natl Acad Sci U S A. 2005;102(44):15791–6. https://doi.org/10.1073/pnas.0507375102.CrossRefPubMedPubMedCentral

81.

Lee J, Warnken U, Schnolzer M, Gebert J, Kopitz J. A new method for detection of tumor driver-dependent changes of protein sialylation in a colon cancer cell line reveals nectin-3 as TGFBR2 target. Protein Sci. 2015;24(10):1686–94. https://doi.org/10.1002/pro.2741.CrossRefPubMedPubMedCentral

82.

Wildt S, Gerngross TU. The humanization of N-glycosylation pathways in yeast. Nat Rev Microbiol. 2005;3(2):119–28. https://doi.org/10.1038/nrmicro1087.CrossRefPubMed

83.

Aebi M. N-linked protein glycosylation in the ER. Biochim Biophys Acta. 1833;2013:2430–7.

84.

Bailey UM, Schulz BL. Deglycosylation systematically improves N-glycoprotein identification in liquid chromatography-tandem mass spectrometry proteomics for analysis of cell wall stress responses in Saccharomyces cerevisiae lacking Alg3p. J Chromatogr B Analyt Technol Biomed Life Sci. 2013;923–924:16–21.CrossRefPubMed

85.

Jeong Y, Hoang NT, Lovejoy A, Stehr H, Newman AM, Gentles AJ, et al. Role of KEAP1/NRF2 and TP53 mutations in lung squamous cell carcinoma development and radiation resistance. Cancer Discov. 2017;7(1):86–101. https://doi.org/10.1158/2159-8290.CD-16-0127.CrossRefPubMed

86.

Biddlestone-Thorpe L, Sajjad M, Rosenberg E, Beckta JM, Valerie NC, Tokarz M, et al. ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation. Clin Cancer Res. 2013;19(12):3189–200. https://doi.org/10.1158/1078-0432.CCR-12-3408.CrossRefPubMedPubMedCentral

87.

Skinner HD, Sandulache VC, Ow TJ, Meyn RE, Yordy JS, Beadle BM, et al. TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence. Clin Cancer Res. 2012;18(1):290–300. https://doi.org/10.1158/1078-0432.CCR-11-2260.CrossRefPubMed

Title: ALG3 contributes to stemness and radioresistance through regulating glycosylation of TGF-β receptor II in breast cancer
Authors: Xiaoqing Sun
Zhenyu He
Ling Guo
Caiqin Wang
Chuyong Lin
Liping Ye
Xiaoqing Wang
Yue Li
Meisongzhu Yang
Sailan Liu
Xin Hua
Wen Wen
Chao Lin
Zhiqing Long
Wenwen Zhang
Han Li
Yunting Jian
Ziyuan Zhu
Xianqiu Wu
Huanxin Lin
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Radiotherapy
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-01932-8

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Abstract

Background

Methods

Results

Conclusion

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