Functional interaction between receptor tyrosine kinase MET and ETS transcription factors promotes prostate cancer progression.
Capmatinib
ETS transcription factors
MET signalling
prostate cancer
transcriptomic analysis
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
07 Oct 2024
07 Oct 2024
Historique:
revised:
29
07
2024
received:
23
11
2023
accepted:
15
08
2024
medline:
7
10
2024
pubmed:
7
10
2024
entrez:
7
10
2024
Statut:
aheadofprint
Résumé
Prostate cancer, the most common malignancy in men, has a relatively favourable prognosis. However, when it spreads to the bone, the survival rate drops dramatically. The development of bone metastases leaves patients with aggressive prostate cancer, the leading cause of death in men. Moreover, bone metastases are incurable and very painful. Hepatocyte growth factor receptor (MET) and fusion of genes encoding E26 transformation-specific (ETS) transcription factors are both involved in the progression of the disease. ETS gene fusions, in particular, have the ability to induce the migratory and invasive properties of prostate cancer cells, whereas MET receptor, through its signalling cascades, is able to activate transcription factor expression. MET signalling and ETS gene fusions are intimately linked to high-grade prostate cancer. However, the collaboration of these factors in prostate cancer progression has not yet been investigated. Here, we show, using cell models of advanced prostate cancer, that ETS translocation variant 1 (ETV1) and transcriptional regulator ERG (ERG) transcription factors (members of the ETS family) promote tumour properties, and that activation of MET signalling enhances these effects. By using a specific MET tyrosine kinase inhibitor in a humanised hepatocyte growth factor (HGF) mouse model, we also establish that MET activity is required for ETV1/ERG-mediated tumour growth. Finally, by performing a comparative transcriptomic analysis, we identify target genes that could play a relevant role in these cellular processes. Thus, our results demonstrate for the first time in prostate cancer models a functional interaction between ETS transcription factors (ETV1 and ERG) and MET signalling that confers more aggressive properties and highlight a molecular signature characteristic of this combined action.
Identifiants
pubmed: 39374163
doi: 10.1002/1878-0261.13739
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
Graham LS, Lin JK, Lage DE, Kessler ER, Parikh RB, Morgans AK. Management of prostate cancer in older adults. Am Soc Clin Oncol Educ Book. 2023;43:e390396.
Stangelberger A, Waldert M, Djavan B. Prostate cancer in elderly men. Rev Urol. 2008;10(2):111–119.
Panorama des cancers_2023.pdf. https://www.e-cancer.fr/Expertises-et-publications/Catalogue-des-publications/Panorama-des-cancers-en-France-edition-2023
Shiota M, Akamatsu S, Tsukahara S, Nagakawa S, Matsumoto T, Eto M. Androgen receptor mutations for precision medicine in prostate cancer. Endocr Relat Cancer. 2022;29(10):R143–R155.
Coleman RE, Croucher PI, Padhani AR, Clézardin P, Chow E, Fallon M, et al. Bone metastases. Nat Rev Dis Primers. 2020;6(1):83.
Sartor O, De Bono JS. Metastatic Prostate Cancer. N Engl J Med. 2018;378(7):645–657.
Park SH, Eber MR, Shiozawa Y. Models of prostate cancer bone metastasis. Methods Mol Biol. 2019;1914:295–308.
Jané‐Valbuena J, Widlund HR, Perner S, Johnson LA, Dibner AC, Lin WM, et al. An oncogenic role for ETV1 in melanoma. Cancer Res. 2010;70(5):2075–2084.
Yen CC, Chen LT, Li CF, Chen SC, Chua WY, Lin YC, et al. Identification of phenothiazine as an ETV1‐targeting agent in gastrointestinal stromal tumors using the connectivity map. Int J Oncol. 2019;55(2):536–546.
Qu H, Zhao H, Zhang X, Liu Y, Li F, Sun L, et al. Integrated analysis of the ETS family in melanoma reveals a regulatory role of ETV7 in the immune microenvironment. Front Immunol. 2020;11:612784.
Apfelbaum AA, Wrenn ED, Lawlor ER. The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: a review. Front Oncol. 2022;12:1044707.
Firlej V, Ladam F, Brysbaert G, Dumont P, Fuks F, de Launoit Y, et al. Reduced tumorigenesis in mouse mammary cancer cells following inhibition of Pea3‐ or erm‐dependent transcription. J Cell Sci. 2008;121(20):3393–3402.
Yamamoto H, Horiuchi S, Adachi Y, Taniguchi H, Nosho K, Min Y, et al. Expression of ets‐related transcriptional factor E1AF is associated with tumor progression and over‐expression of matrilysin in human gastric cancer. Carcinogenesis. 2004;25(3):325–332.
Dumortier M, Ladam F, Damour I, Vacher S, Bièche I, Marchand N, et al. ETV4 transcription factor and MMP13 metalloprotease are interplaying actors of breast tumorigenesis. Breast Cancer Res. 2018;20:73.
Firlej V, Bocquet B, Desbiens X, de Launoit Y, Chotteau‐Lelièvre A. Pea3 transcription factor cooperates with USF‐1 in regulation of the murine bax transcription without binding to an Ets‐binding site*. J Biol Chem. 2005;280(2):887–898.
Subbaramaiah K, Norton L, Gerald W, Dannenberg AJ. Cyclooxygenase‐2 is overexpressed in HER‐2/neu‐positive breast cancer. J Biol Chem. 2002;277(21):18649–18657.
Ladam F, Damour I, Dumont P, Kherrouche Z, de Launoit Y, Tulasne D, et al. Loss of a negative feedback loop involving Pea3 and cyclin D2 is required for Pea3‐induced migration in transformed mammary epithelial cells. Mol Cancer Res. 2013;11(11):1412–1424.
de Launoit Y, Baert JL, Chotteau‐Lelievre A, Monte D, Coutte L, Mauen S, et al. The Ets transcription factors of the PEA3 group: transcriptional regulators in metastasis. Biochimica et Biophysica Acta. 1766;2006(1):79–87.
Tian TV, Tomavo N, Huot L, Flourens A, Bonnelye E, Flajollet S, et al. Identification of novel TMPRSS2:ERG mechanisms in prostate cancer metastasis: involvement of MMP9 and PLXNA2. Oncogene. 2014;33(17):2204–2214.
Tomlins SA. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310(5748):644–648.
Rubin MA, Maher CA, Chinnaiyan AM. Common gene rearrangements in prostate cancer. J Clin Oncol. 2011;29(27):3659–3668.
Tomlins SA, Laxman B, Varambally S, Cao X, Yu J, Helgeson BE, et al. Role of the TMPRSS2‐ERG gene fusion in prostate cancer. Neoplasia. 2008;10(2):177–188.
Cai C, Hsieh CL, Omwancha J, Zheng Z, Chen SY, Baert JL, et al. ETV1 is a novel androgen receptor‐regulated gene that mediates prostate cancer cell invasion. Mol Endocrinol. 2007;21(8):1835–1846.
Deplus R, Delliaux C, Marchand N, Flourens A, Vanpouille N, Leroy X, et al. TMPRSS2‐ERG fusion promotes prostate cancer metastases in bone. Oncotarget. 2016;8(7):11827–11840.
Alder D, Braun M, Nikolov P, Boehm D, Scheble V, Menon R, et al. Rearrangement of the ETS genes ETV‐1, ETV‐4, ETV‐5, and ELK‐4 is a clonal event during prostate cancer progression. Hum Pathol. 2012;43(11):1910–1916.
Ponzetto C, Bardelli A, Zhen Z, Maina F, dalla Zonca P, Giordano S, et al. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell. 1994;77(2):261–271.
Moumen A, Ieraci A, Patané S, Solé C, Comella JX, Dono R, et al. Met signals hepatocyte survival by preventing Fas‐triggered FLIP degradation in a PI3k‐Akt‐dependent manner. Hepatology. 2007;45(5):1210–1217.
Fernandes M, Jamme P, Cortot AB, Kherrouche Z, Tulasne D. When the MET receptor kicks in to resist targeted therapies. Oncogene. 2021;40(24):4061–4078.
Fixman ED, Fournier TM, Kamikura DM, Naujokas MA, Park M. Pathways downstream of Shc and Grb2 are required for cell transformation by the Tpr‐met oncoprotein*. J Biol Chem. 1996;271(22):13116–13122.
Johnson GL, Lapadat R. Mitogen‐activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002;298(5600):1911–1912.
Sy T, Yl H, Wh Y, Ch T. Hepatocyte growth factor‐induced BMP‐2 expression is mediated by c‐met receptor, FAK, JNK, Runx2, and p300 pathways in human osteoblasts. Int Immunopharmacol. 2012;13(2):156–162.
Tsou H‐K, Chen HT, Hung YH, Chang CH, Li TM, Fong YC, et al. HGF and c‐met interaction promotes migration in human chondrosarcoma cells. PLoS One. 2013;8(1):e53974.
Chang L, Hu Y, Fu Y, Zhou T, You J, du J, et al. Targeting slug‐mediated non‐canonical activation of c‐met to overcome chemo‐resistance in metastatic ovarian cancer cells. Acta Pharm Sin B. 2019;9(3):484–495.
Dong Y, Xu J, Sun B, Wang J, Wang Z. MET‐targeted therapies and clinical outcomes: a systematic literature review. Mol Diagn Ther. 2022;26(2):203–227.
Delord J‐P, Argilés G, Fayette J, Wirth L, Kasper S, Siena S, et al. A phase 1b study of the MET inhibitor capmatinib combined with cetuximab in patients with MET‐positive colorectal cancer who had progressed following anti‐EGFR monoclonal antibody treatment. Investig New Drugs. 2020;38:1774–1783.
Schuler M, Berardi R, Lim WT, de Jonge M, Bauer TM, Azaro A, et al. Molecular correlates of response to capmatinib in advanced non‐small‐cell lung cancer: clinical and biomarker results from a phase I trial. Ann Oncol. 2020;31(6):789–797.
Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, et al. Phase Ib/II study of Capmatinib (INC280) plus gefitinib after failure of epidermal growth factor receptor (EGFR) inhibitor therapy in patients with EGFR‐mutated, MET factor–dysregulated non–small‐cell lung cancer. JCO. 2018;36(31):3101–3109.
Winnes M, Lissbrant E, Damber J‐E, Stenman G. Molecular genetic analyses of the TMPRSS2‐ERG and TMPRSS2‐ETV1 gene fusions in 50 cases of prostate cancer. Oncol Rep. 2007;17(5):1033–1036.
Cerveira N, Ribeiro FR, Peixoto A, Costa V, Henrique R, Jerönimo C, et al. TMPRSS2‐ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. Neoplasia. 2006;8(10):826–832.
Perner S, Mosquera JM, Demichelis F, Hofer MD, Paris PL, Simko J, et al. TMPRSS2‐ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol. 2007;31(6):882–888.
Wang J, Cai Y, Ren C, Ittmann M. Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. Cancer Res. 2006;66(17):8347–8351.
Tripathi A, Supko JG, Gray KP, Melnick ZJ, Regan MM, Taplin ME, et al. Dual blockade of c‐MET and the androgen receptor in metastatic castration‐resistant prostate cancer: a phase 1 study of concurrent enzalutamide and Crizotinib. Clin Cancer Res. 2020;26(23):6122–6131.
Zhang T, Wang Y, Xie M, Ji X, Luo X, Chen X, et al. HGF‐mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c‐MET. J Exp Clin Cancer Res. 2022;41:275.
Gu M‐L, Zhou XX, Ren MT, Shi KD, Yu MS, Jiao WR, et al. Blockage of ETS homologous factor inhibits the proliferation and invasion of gastric cancer cells through the c‐met pathway. World J Gastroenterol. 2020;26(47):7497–7512.
Selvaraj N, Budka JA, Ferris MW, Jerde TJ, Hollenhorst PC. Prostate cancer ETS rearrangements switch a cell migration gene expression program from RAS/ERK to PI3K/AKT regulation. Mol Cancer. 2014;13(1):61.
Kherrouche Z, Monte D, Werkmeister E, Stoven L, de Launoit Y, Cortot AB, et al. PEA3 transcription factors are downstream effectors of met signaling involved in migration and invasiveness of met‐addicted tumor cells. Mol Oncol. 2015;9(9):1852–1867.
Hariss F, Delbeke M, Guyot K, Zarnitzky P, Ezzedine M, Certad G, et al. Cytotoxic innate intraepithelial lymphocytes control early stages of cryptosporidium infection. Front Immunol. 2023;14:1229406.
Dong L, Zieren RC, Xue W, de Reijke TM, Pienta KJ. Metastatic prostate cancer remains incurable, why? Asian J Urol. 2019;6(1):26–41.
Carver BS, Tran J, Chen Z, Carracedo‐Perez A, Alimonti A, Nardella C, et al. ETS genetic rearrangements do not initiate cancer in the prostate. Nature. 2009;457(7231):E1–E3.
Liu T, Mendes DE, Berkman CE. From AR to c‐met: androgen deprivation leads to a signaling pathway switch in prostate cancer cells. Int J Oncol. 2013;43(4):1125–1130.
Gambarotta G, Boccaccio C, Giordano S, Andŏ M, Stella M, Comoglio P. ETS up‐regulates MET transcription. Oncogene. 1996;13:1911–1917.
Saeki H, Oda S, Kawaguchi H, Ohno S, Kuwano H, Maehara Y, et al. Concurrent overexpression of ETS‐1 and C‐met correlates with a phenotype of high cellular motility in human esophageal cancer. Int J Cancer. 2002;98(1):8–13.
Kubic JD, Little EC, Lui JW, Iizuka T, Lang D. PAX3 and ETS1 synergistically activate MET expression in melanoma cells. Oncogene. 2015;34(38):4964–4974.
Breunig C, Erdem N, Bott A, Greiwe JF, Reinz E, Bernhardt S, et al. TGFβ1 regulates HGF‐induced cell migration and hepatocyte growth factor receptor MET expression via C‐ets‐1 and miR‐128‐3p in basal‐like breast cancer. Mol Oncol. 2018;12(9):1447–1463.
He Y, Luo W, Liu Y, Wang Y, Ma C, Wu Q, et al. IL‐20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer. J Clin Invest. 2022;132(20):e157917.
Li Y, Chen R, Li Z, Cheng H, Li X, Li T, et al. miR‐204 negatively regulates cell growth and metastasis by targeting ROBO4 in human bladder cancer. Onco Targets Ther. 2019;12:8515–8524.
Turkowski K, Herzberg F, Günther S, Brunn D, Weigert A, Meister M, et al. Fibroblast growth factor—14 acts as tumor suppressor in lung adenocarcinomas. Cells. 2020;9(8):1755.
Heidegger I, Fotakis G, Offermann A, Goveia J, Daum S, Salcher S, et al. Comprehensive characterization of the prostate tumor microenvironment identifies CXCR4/CXCL12 crosstalk as a novel antiangiogenic therapeutic target in prostate cancer. Mol Cancer. 2022;21(1):132.
Yang S, Li WS, Dong F, Sun HM, Wu B, Tan J, et al. KITLG is a novel target of miR‐34c that is associated with the inhibition of growth and invasion in colorectal cancer cells. J Cell Mol Med. 2014;18(10):2092–2102.
Wang L, Wang L, Zhang H, Lu J, Zhang Z, Wu H, et al. AREG mediates the epithelial‐mesenchymal transition in pancreatic cancer cells via the EGFR/ERK/NF‐κB signalling pathway. Oncol Rep. 2020;43(5):1558–1568.
Liu J, Pan L, Hong W, Chen S, Bai P, Luo W, et al. GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression. Nat Commun. 2022;13:7519.
Berasain C, Avila MA. Amphiregulin. Semin Cell Dev Biol. 2014;28:31–41.
Wang C‐Q, Huang YW, Wang SW, Huang YL, Tsai CH, Zhao YM, et al. Amphiregulin enhances VEGF‐A production in human chondrosarcoma cells and promotes angiogenesis by inhibiting miR‐206 via FAK/c‐Src/PKCδ pathway. Cancer Lett. 2017;385:261–270.
Kim JH, Kim K, Jin HM, Youn BU, Song I, Choi HS, et al. Upstream stimulatory factors regulate OSCAR gene expression in RANKL‐mediated osteoclast differentiation. J Mol Biol. 2008;383(3):502–511.
Nedeva IR, Vitale M, Elson A, Hoyland JA, Bella J. Role of OSCAR signaling in Osteoclastogenesis and bone disease. Front Cell Dev Biol. 2021;9:641162.
Liao X, Bu Y, Zhang Y, Xu B, Liang J, Jia Q, et al. OSCAR facilitates malignancy with enhanced metastasis correlating to inhibitory immune microenvironment in multiple cancer types. J Cancer. 2021;12(13):3769–3780.
Attard G, Jameson C, Moreira J, Flohr P, Parker C, Dearnaley D, et al. Hormone‐sensitive prostate cancer: a case of ETS gene fusion heterogeneity. J Clin Pathol. 2009;62(4):373–376.