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Published in: Journal of Translational Medicine 1/2024

Open Access 01-12-2024 | Ovarian Cancer | Research

Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter

Authors: Songwei Feng, Bo Ding, Zhu Dai, Han Yin, Yue Ding, Sicong Liu, Ke Zhang, Hao Lin, Zhongdang Xiao, Yang Shen

Published in: Journal of Translational Medicine | Issue 1/2024

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Abstract

Background

Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression.

Methods

Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as a potential oncogenic factor. We investigated the relationship between FGF7 expression and various clinical parameters. A series of in vitro experiments were undertaken to evaluate the effect of CAFs-derived FGF7 on OC cell activities, such as proliferation, migration, and invasion. Single-cell transcriptomic analysis was also conducted to elucidate the interaction between FGF7 and its receptor. Detailed mechanistic investigations sought to clarify the pathways through which FGF7 fosters OC progression.

Results

Our findings indicate that higher FGF7 levels correlate with advanced tumor stages, increased vascular invasion, and poorer prognosis. CAFs-derived FGF7 significantly enhanced OC cell proliferation, migration, and invasion. Single-cell analysis and in vitro studies revealed that CAFs-derived FGF7 inhibits the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF-1α) via FGFR2 interaction. Activation of the FGF7/HIF-1α pathway resulted in the upregulation of mesenchymal markers and downregulation of epithelial markers. Importantly, in vivo treatment with neutralizing antibodies targeting CAFs-derived FGF7 substantially reduced tumor growth.

Conclusion

Neutralizing FGF7 in the medium or inhibiting HIF-1α signaling reversed the effects of FGF7-mediated EMT, emphasizing the dependence of FGF7-mediated EMT on HIF-1α activation. These findings suggest that targeting the FGF7/HIF-1α/EMT axis may offer new therapeutic opportunities to intervene in OC progression.
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Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(2018):394–424.PubMedCrossRef Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(2018):394–424.PubMedCrossRef
3.
go back to reference Feng S, Xu Y, Dai Z, Yin H, Zhang K, Shen Y. Integrative analysis from multicenter studies identifies a WGCNA-derived cancer-associated fibroblast signature for ovarian cancer. Front Immunol. 2022;13: 951582.PubMedPubMedCentralCrossRef Feng S, Xu Y, Dai Z, Yin H, Zhang K, Shen Y. Integrative analysis from multicenter studies identifies a WGCNA-derived cancer-associated fibroblast signature for ovarian cancer. Front Immunol. 2022;13: 951582.PubMedPubMedCentralCrossRef
4.
go back to reference Wang Y, Chen Z, Zhao G, Li Q. Cancer-associated fibroblast risk model for prediction of colorectal carcinoma prognosis and therapeutic responses. Mediators Inflamm. 2023;2023:3781091.PubMedPubMedCentralCrossRef Wang Y, Chen Z, Zhao G, Li Q. Cancer-associated fibroblast risk model for prediction of colorectal carcinoma prognosis and therapeutic responses. Mediators Inflamm. 2023;2023:3781091.PubMedPubMedCentralCrossRef
5.
go back to reference Wang S, Fan G, Li L, He Y, Lou N, Xie T, Dai L, Gao R, Yang M, Shi Y, Han X. Integrative analyses of bulk and single-cell RNA-seq identified cancer-associated fibroblasts-related signature as a prognostic factor for immunotherapy in NSCLC. Cancer Immunol Immunother. 2023;72:2423–42.PubMedCrossRef Wang S, Fan G, Li L, He Y, Lou N, Xie T, Dai L, Gao R, Yang M, Shi Y, Han X. Integrative analyses of bulk and single-cell RNA-seq identified cancer-associated fibroblasts-related signature as a prognostic factor for immunotherapy in NSCLC. Cancer Immunol Immunother. 2023;72:2423–42.PubMedCrossRef
7.
go back to reference Galbo PM Jr, Zang X, Zheng D. Molecular features of cancer-associated fibroblast subtypes and their implication on cancer pathogenesis, prognosis, and immunotherapy resistance. Clin Cancer Res. 2021;27:2636–47.PubMedPubMedCentralCrossRef Galbo PM Jr, Zang X, Zheng D. Molecular features of cancer-associated fibroblast subtypes and their implication on cancer pathogenesis, prognosis, and immunotherapy resistance. Clin Cancer Res. 2021;27:2636–47.PubMedPubMedCentralCrossRef
8.
go back to reference Hegab AE, Ozaki M, Kameyama N, Gao J, Kagawa S, Yasuda H, Soejima K, Yin Y, Guzy RD, Nakamura Y, Ornitz DM, Betsuyaku T. Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer-associated fibroblasts. J Pathol. 2019;249:193–205.PubMedCrossRef Hegab AE, Ozaki M, Kameyama N, Gao J, Kagawa S, Yasuda H, Soejima K, Yin Y, Guzy RD, Nakamura Y, Ornitz DM, Betsuyaku T. Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer-associated fibroblasts. J Pathol. 2019;249:193–205.PubMedCrossRef
9.
go back to reference Eckert MA, Coscia F, Chryplewicz A, Chang JW, Hernandez KM, Pan S, Tienda SM, Nahotko DA, Li G, Blazenovic I, Lastra RR, Curtis M, Yamada SD, Perets R, McGregor SM, Andrade J, Fiehn O, Moellering RE, Mann M, Lengyel E. Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts. Nature. 2019;569:723–8.PubMedPubMedCentralCrossRefADS Eckert MA, Coscia F, Chryplewicz A, Chang JW, Hernandez KM, Pan S, Tienda SM, Nahotko DA, Li G, Blazenovic I, Lastra RR, Curtis M, Yamada SD, Perets R, McGregor SM, Andrade J, Fiehn O, Moellering RE, Mann M, Lengyel E. Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts. Nature. 2019;569:723–8.PubMedPubMedCentralCrossRefADS
10.
go back to reference Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P. The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol. 2010;10:554–67.PubMedCrossRef Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P. The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol. 2010;10:554–67.PubMedCrossRef
11.
go back to reference Ko SY, Barengo N, Ladanyi A, Lee JS, Marini F, Lengyel E, Naora H. HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts. J Clin Invest. 2012;122:3603–17.PubMedPubMedCentralCrossRef Ko SY, Barengo N, Ladanyi A, Lee JS, Marini F, Lengyel E, Naora H. HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts. J Clin Invest. 2012;122:3603–17.PubMedPubMedCentralCrossRef
12.
go back to reference Deying W, Feng G, Shumei L, Hui Z, Ming L, Hongqing W. CAF-derived HGF promotes cell proliferation and drug resistance by up-regulating the c-Met/PI3K/Akt and GRP78 signalling in ovarian cancer cells. 2017. Biosci Rep. https://doi.org/10.1042/BSR20160470. Deying W, Feng G, Shumei L, Hui Z, Ming L, Hongqing W. CAF-derived HGF promotes cell proliferation and drug resistance by up-regulating the c-Met/PI3K/Akt and GRP78 signalling in ovarian cancer cells. 2017. Biosci Rep. https://​doi.​org/​10.​1042/​BSR20160470.
13.
go back to reference Gao Q, Yang Z, Xu S, Li X, Yang X, Jin P, Liu Y, Zhou X, Zhang T, Gong C, Wei X, Liu D, Sun C, Chen G, Hu J, Meng L, Zhou J, Sawada K, Fruscio R, Grunt TW, Wischhusen J, Vargas-Hernandez VM, Pothuri B, Coleman RL. Heterotypic CAF-tumor spheroids promote early peritoneal metastatis of ovarian cancer. J Exp Med. 2019;216:688–703.PubMedPubMedCentralCrossRef Gao Q, Yang Z, Xu S, Li X, Yang X, Jin P, Liu Y, Zhou X, Zhang T, Gong C, Wei X, Liu D, Sun C, Chen G, Hu J, Meng L, Zhou J, Sawada K, Fruscio R, Grunt TW, Wischhusen J, Vargas-Hernandez VM, Pothuri B, Coleman RL. Heterotypic CAF-tumor spheroids promote early peritoneal metastatis of ovarian cancer. J Exp Med. 2019;216:688–703.PubMedPubMedCentralCrossRef
14.
go back to reference Zhang R, Qi F, Zhao F, Li G, Shao S, Zhang X, Yuan L, Feng Y. Cancer-associated fibroblasts enhance tumor-associated macrophages enrichment and suppress NK cells function in colorectal cancer. Cell Death Dis. 2019;10:273.PubMedPubMedCentralCrossRef Zhang R, Qi F, Zhao F, Li G, Shao S, Zhang X, Yuan L, Feng Y. Cancer-associated fibroblasts enhance tumor-associated macrophages enrichment and suppress NK cells function in colorectal cancer. Cell Death Dis. 2019;10:273.PubMedPubMedCentralCrossRef
15.
go back to reference Zhang J, Wong CC, Leung KT, Wu F, Zhou Y, Tong JHM, Chan RCK, Li H, Wang Y, Yan H, Liu L, Wu WKK, Chan MWY, Cheng ASL, Yu J, Wong N, Lo KW, To KF, Kang W. FGF18-FGFR2 signaling triggers the activation of c-Jun-YAP1 axis to promote carcinogenesis in a subgroup of gastric cancer patients and indicates translational potential. Oncogene. 2020;39:6647–63.PubMedPubMedCentralCrossRef Zhang J, Wong CC, Leung KT, Wu F, Zhou Y, Tong JHM, Chan RCK, Li H, Wang Y, Yan H, Liu L, Wu WKK, Chan MWY, Cheng ASL, Yu J, Wong N, Lo KW, To KF, Kang W. FGF18-FGFR2 signaling triggers the activation of c-Jun-YAP1 axis to promote carcinogenesis in a subgroup of gastric cancer patients and indicates translational potential. Oncogene. 2020;39:6647–63.PubMedPubMedCentralCrossRef
16.
go back to reference Hua Y, Yin H, Liu X, Xie J, Zhan W, Liang G, Shen Y. Salt-inducible kinase 2-triggered release of its inhibitor from hydrogel to suppress ovarian cancer metastasis. Adv Sci (Weinh). 2022;9: e2202260.PubMedCrossRef Hua Y, Yin H, Liu X, Xie J, Zhan W, Liang G, Shen Y. Salt-inducible kinase 2-triggered release of its inhibitor from hydrogel to suppress ovarian cancer metastasis. Adv Sci (Weinh). 2022;9: e2202260.PubMedCrossRef
17.
go back to reference Lu Y, Chen Y, Hu W, Wang M, Wen X, Yang J. Inhibition of ACSS2 attenuates alcoholic liver steatosis via epigenetically regulating de novo lipogenesis. Liver Int. 2023;43:1729–40.PubMedCrossRef Lu Y, Chen Y, Hu W, Wang M, Wen X, Yang J. Inhibition of ACSS2 attenuates alcoholic liver steatosis via epigenetically regulating de novo lipogenesis. Liver Int. 2023;43:1729–40.PubMedCrossRef
18.
go back to reference Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL, Serova N, Davis S, Soboleva A. NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res. 2013;41:D991–5.PubMedCrossRef Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL, Serova N, Davis S, Soboleva A. NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res. 2013;41:D991–5.PubMedCrossRef
19.
go back to reference Xu J, Fang Y, Chen K, Li S, Tang S, Ren Y, Cen Y, Fei W, Zhang B, Shen Y, Lu W. Single-cell RNA sequencing reveals the tissue architecture in human high-grade serous ovarian cancer. Clin Cancer Res. 2022;28:3590–602.PubMedPubMedCentralCrossRef Xu J, Fang Y, Chen K, Li S, Tang S, Ren Y, Cen Y, Fei W, Zhang B, Shen Y, Lu W. Single-cell RNA sequencing reveals the tissue architecture in human high-grade serous ovarian cancer. Clin Cancer Res. 2022;28:3590–602.PubMedPubMedCentralCrossRef
20.
go back to reference Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, Baglaenko Y, Brenner M, Loh PR, Raychaudhuri S. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods. 2019;16:1289–96.PubMedPubMedCentralCrossRef Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, Baglaenko Y, Brenner M, Loh PR, Raychaudhuri S. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods. 2019;16:1289–96.PubMedPubMedCentralCrossRef
21.
go back to reference Jin S, Guerrero-Juarez CF, Zhang L, Chang I, Ramos R, Kuan CH, Myung P, Plikus MV, Nie Q. Inference and analysis of cell-cell communication using cell chat. Nat Commun. 2021;12:1088.PubMedPubMedCentralCrossRefADS Jin S, Guerrero-Juarez CF, Zhang L, Chang I, Ramos R, Kuan CH, Myung P, Plikus MV, Nie Q. Inference and analysis of cell-cell communication using cell chat. Nat Commun. 2021;12:1088.PubMedPubMedCentralCrossRefADS
22.
go back to reference Wang Z, Jensen MA, Zenklusen JC. A practical guide to The Cancer Genome Atlas (TCGA). Methods Mol Biol. 2016;1418:111–41.PubMedCrossRef Wang Z, Jensen MA, Zenklusen JC. A practical guide to The Cancer Genome Atlas (TCGA). Methods Mol Biol. 2016;1418:111–41.PubMedCrossRef
23.
go back to reference Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012;28:882–3.PubMedPubMedCentralCrossRef Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012;28:882–3.PubMedPubMedCentralCrossRef
24.
go back to reference Zeng D, Ye Z, Shen R, Yu G, Wu J, Xiong Y, Zhou R, Qiu W, Huang N, Sun L, Li X, Bin J, Liao Y, Shi M, Liao W. IOBR: multi-omics immuno-oncology biological research to decode tumor microenvironment and signatures. Front Immunol. 2021;12: 687975.PubMedPubMedCentralCrossRef Zeng D, Ye Z, Shen R, Yu G, Wu J, Xiong Y, Zhou R, Qiu W, Huang N, Sun L, Li X, Bin J, Liao Y, Shi M, Liao W. IOBR: multi-omics immuno-oncology biological research to decode tumor microenvironment and signatures. Front Immunol. 2021;12: 687975.PubMedPubMedCentralCrossRef
25.
go back to reference Zhao W, Langfelder P, Fuller T, Dong J, Li A, Hovarth S. Weighted gene coexpression network analysis: state of the art. J Biopharm Stat. 2010;20:281–300.MathSciNetPubMedCrossRef Zhao W, Langfelder P, Fuller T, Dong J, Li A, Hovarth S. Weighted gene coexpression network analysis: state of the art. J Biopharm Stat. 2010;20:281–300.MathSciNetPubMedCrossRef
26.
go back to reference Hu JY, Wang Y, Tong XM, Yang T. When to consider logistic LASSO regression in multivariate analysis? Eur J Surg Oncol. 2021;47:2206.PubMedCrossRef Hu JY, Wang Y, Tong XM, Yang T. When to consider logistic LASSO regression in multivariate analysis? Eur J Surg Oncol. 2021;47:2206.PubMedCrossRef
27.
go back to reference Binder H, Allignol A, Schumacher M, Beyersmann J. Boosting for high-dimensional time-to-event data with competing risks. Bioinformatics. 2009;25:890–6.PubMedCrossRef Binder H, Allignol A, Schumacher M, Beyersmann J. Boosting for high-dimensional time-to-event data with competing risks. Bioinformatics. 2009;25:890–6.PubMedCrossRef
29.
go back to reference Zhou J, Lee S, Liu Y, Chan JSK, Li G, Wong WT, Jeevaratnam K, Cheng SH, Liu T, Tse G, Zhang Q. Predicting stroke and mortality in mitral regurgitation: a machine learning approach. Curr Probl Cardiol. 2023;48: 101464.PubMedCrossRef Zhou J, Lee S, Liu Y, Chan JSK, Li G, Wong WT, Jeevaratnam K, Cheng SH, Liu T, Tse G, Zhang Q. Predicting stroke and mortality in mitral regurgitation: a machine learning approach. Curr Probl Cardiol. 2023;48: 101464.PubMedCrossRef
30.
go back to reference Van Belle V, Pelckmans K, Van Huffel S, Suykens JA. Improved performance on high-dimensional survival data by application of survival-SVM. Bioinformatics. 2011;27:87–94.PubMedCrossRef Van Belle V, Pelckmans K, Van Huffel S, Suykens JA. Improved performance on high-dimensional survival data by application of survival-SVM. Bioinformatics. 2011;27:87–94.PubMedCrossRef
31.
33.
go back to reference Nygard S, Borgan O, Lingjaerde OC, Storvold HL. Partial least squares Cox regression for genome-wide data. Lifetime Data Anal. 2008;14:179–95.MathSciNetPubMedCrossRef Nygard S, Borgan O, Lingjaerde OC, Storvold HL. Partial least squares Cox regression for genome-wide data. Lifetime Data Anal. 2008;14:179–95.MathSciNetPubMedCrossRef
35.
go back to reference Liu Z, Liu L, Weng S, Guo C, Dang Q, Xu H, Wang L, Lu T, Zhang Y, Sun Z, Han X. Machine learning-based integration develops an immune-derived lncRNA signature for improving outcomes in colorectal cancer. Nat Commun. 2022;13:816.PubMedPubMedCentralCrossRefADS Liu Z, Liu L, Weng S, Guo C, Dang Q, Xu H, Wang L, Lu T, Zhang Y, Sun Z, Han X. Machine learning-based integration develops an immune-derived lncRNA signature for improving outcomes in colorectal cancer. Nat Commun. 2022;13:816.PubMedPubMedCentralCrossRefADS
36.
go back to reference Li Y, Niu JH, Wang Y. Machine learning-based neddylation landscape indicates different prognosis and immune microenvironment in endometrial cancer. Front Oncol. 2023;13:1084523.PubMedPubMedCentralCrossRef Li Y, Niu JH, Wang Y. Machine learning-based neddylation landscape indicates different prognosis and immune microenvironment in endometrial cancer. Front Oncol. 2023;13:1084523.PubMedPubMedCentralCrossRef
38.
go back to reference Hanzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinform. 2013;14:7.CrossRef Hanzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinform. 2013;14:7.CrossRef
39.
go back to reference Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.PubMedCrossRef Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.PubMedCrossRef
40.
go back to reference Chen Z, Han F, Du Y, Shi H, Zhou W. Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2023;8:70.PubMedPubMedCentralCrossRef Chen Z, Han F, Du Y, Shi H, Zhou W. Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2023;8:70.PubMedPubMedCentralCrossRef
41.
go back to reference Najafi M, Farhood B, Mortezaee K. Extracellular matrix (ECM) stiffness and degradation as cancer drivers. J Cell Biochem. 2019;120:2782–90.PubMedCrossRef Najafi M, Farhood B, Mortezaee K. Extracellular matrix (ECM) stiffness and degradation as cancer drivers. J Cell Biochem. 2019;120:2782–90.PubMedCrossRef
42.
go back to reference Rashid M, Zadeh LR, Baradaran B, Molavi O, Ghesmati Z, Sabzichi M, Ramezani F. Up-down regulation of HIF-1alpha in cancer progression. Gene. 2021;798: 145796.PubMedCrossRef Rashid M, Zadeh LR, Baradaran B, Molavi O, Ghesmati Z, Sabzichi M, Ramezani F. Up-down regulation of HIF-1alpha in cancer progression. Gene. 2021;798: 145796.PubMedCrossRef
43.
go back to reference Zhu J, Huang Z, Zhang M, Wang W, Liang H, Zeng J, Wu K, Wang X, Hsieh JT, Guo P, Fan J. Erratum: HIF-1alpha promotes ZEB1 expression and EMT in a human bladder cancer lung metastasis animal model. Oncol Lett. 2021;22:599.PubMedPubMedCentralCrossRef Zhu J, Huang Z, Zhang M, Wang W, Liang H, Zeng J, Wu K, Wang X, Hsieh JT, Guo P, Fan J. Erratum: HIF-1alpha promotes ZEB1 expression and EMT in a human bladder cancer lung metastasis animal model. Oncol Lett. 2021;22:599.PubMedPubMedCentralCrossRef
44.
go back to reference Zhang W, Shi X, Peng Y, Wu M, Zhang P, Xie R, Wu Y, Yan Q, Liu S, Wang J. HIF-1alpha promotes epithelial-mesenchymal transition and metastasis through direct regulation of ZEB1 in colorectal cancer. PLoS ONE. 2015;10: e0129603.PubMedPubMedCentralCrossRef Zhang W, Shi X, Peng Y, Wu M, Zhang P, Xie R, Wu Y, Yan Q, Liu S, Wang J. HIF-1alpha promotes epithelial-mesenchymal transition and metastasis through direct regulation of ZEB1 in colorectal cancer. PLoS ONE. 2015;10: e0129603.PubMedPubMedCentralCrossRef
45.
go back to reference Yoshimoto S, Tanaka F, Morita H, Hiraki A, Hashimoto S. Hypoxia-induced HIF-1alpha and ZEB1 are critical for the malignant transformation of ameloblastoma via TGF-beta-dependent EMT. Cancer Med. 2019;8:7822–32.PubMedPubMedCentralCrossRef Yoshimoto S, Tanaka F, Morita H, Hiraki A, Hashimoto S. Hypoxia-induced HIF-1alpha and ZEB1 are critical for the malignant transformation of ameloblastoma via TGF-beta-dependent EMT. Cancer Med. 2019;8:7822–32.PubMedPubMedCentralCrossRef
46.
go back to reference Reel PS, Reel S, Pearson E, Trucco E, Jefferson E. Using machine learning approaches for multi-omics data analysis: a review. Biotechnol Adv. 2021;49: 107739.PubMedCrossRef Reel PS, Reel S, Pearson E, Trucco E, Jefferson E. Using machine learning approaches for multi-omics data analysis: a review. Biotechnol Adv. 2021;49: 107739.PubMedCrossRef
47.
go back to reference Picard M, Scott-Boyer MP, Bodein A, Perin O, Droit A. Integration strategies of multi-omics data for machine learning analysis. Comput Struct Biotechnol J. 2021;19:3735–46.PubMedPubMedCentralCrossRef Picard M, Scott-Boyer MP, Bodein A, Perin O, Droit A. Integration strategies of multi-omics data for machine learning analysis. Comput Struct Biotechnol J. 2021;19:3735–46.PubMedPubMedCentralCrossRef
50.
go back to reference Finch PW, Rubin JS, Miki T, Ron D, Aaronson SA. Human KGF is FGF-related with properties of a paracrine effector of epithelial cell growth. Science. 1989;245:752–5.PubMedCrossRefADS Finch PW, Rubin JS, Miki T, Ron D, Aaronson SA. Human KGF is FGF-related with properties of a paracrine effector of epithelial cell growth. Science. 1989;245:752–5.PubMedCrossRefADS
52.
go back to reference Cui Y, Li Q. Effect of mammogenic hormones on the expression of FGF7, FGF10 and their receptor in mouse mammary gland. Sci China C Life Sci. 2008;51:711–7.PubMedCrossRef Cui Y, Li Q. Effect of mammogenic hormones on the expression of FGF7, FGF10 and their receptor in mouse mammary gland. Sci China C Life Sci. 2008;51:711–7.PubMedCrossRef
53.
go back to reference Zheng C, Cotrim AP, Rowzee A, Swaim W, Sowers A, Mitchell JB, Baum BJ. Prevention of radiation-induced salivary hypofunction following hKGF gene delivery to murine submandibular glands. Clin Cancer Res. 2011;17:2842–51.PubMedPubMedCentralCrossRef Zheng C, Cotrim AP, Rowzee A, Swaim W, Sowers A, Mitchell JB, Baum BJ. Prevention of radiation-induced salivary hypofunction following hKGF gene delivery to murine submandibular glands. Clin Cancer Res. 2011;17:2842–51.PubMedPubMedCentralCrossRef
54.
go back to reference Wirth K, Mertelsmann R. Cytoprotective function of keratinocyte growth factor in tumour therapy-induced tissue damage. Br J Haematol. 2002;116:505–10.PubMedCrossRef Wirth K, Mertelsmann R. Cytoprotective function of keratinocyte growth factor in tumour therapy-induced tissue damage. Br J Haematol. 2002;116:505–10.PubMedCrossRef
55.
go back to reference Li J, Lu R, Yang K, Sun Q. circCCT3 enhances invasion and epithelial-mesenchymal transition (EMT) of non-small-cell lung cancer (NSCLC) via the miR-107/Wnt/FGF7 axis. J Oncol. 2022;2022:7020774.PubMedPubMedCentral Li J, Lu R, Yang K, Sun Q. circCCT3 enhances invasion and epithelial-mesenchymal transition (EMT) of non-small-cell lung cancer (NSCLC) via the miR-107/Wnt/FGF7 axis. J Oncol. 2022;2022:7020774.PubMedPubMedCentral
56.
go back to reference Fan EW, Li CC, Wu WJ, Huang CN, Li WM, Ke HL, Yeh HC, Wu TF, Liang PI, Ma LJ, Li CF. FGF7 over expression is an independent prognosticator in patients with urothelial carcinoma of the upper urinary tract and bladder. J Urol. 2015;194:223–9.PubMedCrossRef Fan EW, Li CC, Wu WJ, Huang CN, Li WM, Ke HL, Yeh HC, Wu TF, Liang PI, Ma LJ, Li CF. FGF7 over expression is an independent prognosticator in patients with urothelial carcinoma of the upper urinary tract and bladder. J Urol. 2015;194:223–9.PubMedCrossRef
57.
go back to reference Zhu Y, Yang L, Chong QY, Yan H, Zhang W, Qian W, Tan S, Wu Z, Lobie PE, Zhu T. Long noncoding RNA Linc00460 promotes breast cancer progression by regulating the miR-489-5p/FGF7/AKT axis. Cancer Manag Res. 2019;11:5983–6001.PubMedPubMedCentralCrossRef Zhu Y, Yang L, Chong QY, Yan H, Zhang W, Qian W, Tan S, Wu Z, Lobie PE, Zhu T. Long noncoding RNA Linc00460 promotes breast cancer progression by regulating the miR-489-5p/FGF7/AKT axis. Cancer Manag Res. 2019;11:5983–6001.PubMedPubMedCentralCrossRef
58.
go back to reference Liu Z, Liu J, Chen T, Wang Y, Shi A, Li K, Li X, Qiu B, Zheng L, Zhao L, Shu L, Lian S, Huang S, Zhang Z, Xu Y. Wnt-TCF7-SOX9 axis promotes cholangiocarcinoma proliferation and pemigatinib resistance in a FGF7-FGFR2 autocrine pathway. Oncogene. 2022;41:2885–96.PubMedCrossRef Liu Z, Liu J, Chen T, Wang Y, Shi A, Li K, Li X, Qiu B, Zheng L, Zhao L, Shu L, Lian S, Huang S, Zhang Z, Xu Y. Wnt-TCF7-SOX9 axis promotes cholangiocarcinoma proliferation and pemigatinib resistance in a FGF7-FGFR2 autocrine pathway. Oncogene. 2022;41:2885–96.PubMedCrossRef
59.
go back to reference Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006;281:15694–700.PubMedCrossRef Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006;281:15694–700.PubMedCrossRef
60.
go back to reference Mason IJ, Fuller-Pace F, Smith R, Dickson C. FGF-7 (keratinocyte growth factor) expression during mouse development suggests roles in myogenesis, forebrain regionalisation and epithelial-mesenchymal interactions. Mech Dev. 1994;45:15–30.PubMedCrossRef Mason IJ, Fuller-Pace F, Smith R, Dickson C. FGF-7 (keratinocyte growth factor) expression during mouse development suggests roles in myogenesis, forebrain regionalisation and epithelial-mesenchymal interactions. Mech Dev. 1994;45:15–30.PubMedCrossRef
61.
go back to reference Mieczkowski K, Kitowska K, Braun M, Galikowska-Bogut B, Gorska-Arcisz M, Piasecka D, Stawiski K, Zaczek AJ, Nejc D, Kordek R, Romanska HM, Sadej R. FGF7/FGFR2-JunB signalling counteracts the effect of progesterone in luminal breast cancer. Mol Oncol. 2022;16:2823–42.PubMedPubMedCentralCrossRef Mieczkowski K, Kitowska K, Braun M, Galikowska-Bogut B, Gorska-Arcisz M, Piasecka D, Stawiski K, Zaczek AJ, Nejc D, Kordek R, Romanska HM, Sadej R. FGF7/FGFR2-JunB signalling counteracts the effect of progesterone in luminal breast cancer. Mol Oncol. 2022;16:2823–42.PubMedPubMedCentralCrossRef
62.
go back to reference Milton CI, Selfe J, Aladowicz E, Man SYK, Bernauer C, Missiaglia E, Walters ZS, Gatz SA, Kelsey A, Generali M, Box G, Valenti M, de Haven-Brandon A, Galiwango D, Hayes A, Clarke M, Izquierdo E, Gonzalez De Castro D, Raynaud FI, Kirkin V, Shipley JM. FGF7-FGFR2 autocrine signaling increases growth and chemoresistance of fusion-positive rhabdomyosarcomas. Mol Oncol. 2022;16:1272–89.PubMedCrossRef Milton CI, Selfe J, Aladowicz E, Man SYK, Bernauer C, Missiaglia E, Walters ZS, Gatz SA, Kelsey A, Generali M, Box G, Valenti M, de Haven-Brandon A, Galiwango D, Hayes A, Clarke M, Izquierdo E, Gonzalez De Castro D, Raynaud FI, Kirkin V, Shipley JM. FGF7-FGFR2 autocrine signaling increases growth and chemoresistance of fusion-positive rhabdomyosarcomas. Mol Oncol. 2022;16:1272–89.PubMedCrossRef
63.
go back to reference Jin Y, Bian S, Wang H, Mo J, Fei H, Li L, Chen T, Jiang H. CRMP2 derived from cancer associated fibroblasts facilitates progression of ovarian cancer via HIF-1alpha-glycolysis signaling pathway. Cell Death Dis. 2022;13:675.PubMedPubMedCentralCrossRef Jin Y, Bian S, Wang H, Mo J, Fei H, Li L, Chen T, Jiang H. CRMP2 derived from cancer associated fibroblasts facilitates progression of ovarian cancer via HIF-1alpha-glycolysis signaling pathway. Cell Death Dis. 2022;13:675.PubMedPubMedCentralCrossRef
65.
go back to reference Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20:69–84.PubMedCrossRef Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20:69–84.PubMedCrossRef
66.
go back to reference Krebs AM, Mitschke J, Lasierra Losada M, Schmalhofer O, Boerries M, Busch H, Boettcher M, Mougiakakos D, Reichardt W, Bronsert P, Brunton VG, Pilarsky C, Winkler TH, Brabletz S, Stemmler MP, Brabletz T. The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol. 2017;19:518–29.PubMedCrossRef Krebs AM, Mitschke J, Lasierra Losada M, Schmalhofer O, Boerries M, Busch H, Boettcher M, Mougiakakos D, Reichardt W, Bronsert P, Brunton VG, Pilarsky C, Winkler TH, Brabletz S, Stemmler MP, Brabletz T. The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol. 2017;19:518–29.PubMedCrossRef
67.
go back to reference Mohammadi Ghahhari N, Sznurkowska MK, Hulo N, Bernasconi L, Aceto N, Picard D. Cooperative interaction between ERalpha and the EMT-inducer ZEB1 reprograms breast cancer cells for bone metastasis. Nat Commun. 2022;13:2104.PubMedPubMedCentralCrossRefADS Mohammadi Ghahhari N, Sznurkowska MK, Hulo N, Bernasconi L, Aceto N, Picard D. Cooperative interaction between ERalpha and the EMT-inducer ZEB1 reprograms breast cancer cells for bone metastasis. Nat Commun. 2022;13:2104.PubMedPubMedCentralCrossRefADS
Metadata
Title
Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter
Authors
Songwei Feng
Bo Ding
Zhu Dai
Han Yin
Yue Ding
Sicong Liu
Ke Zhang
Hao Lin
Zhongdang Xiao
Yang Shen
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2024
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-024-05085-y

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