RON and c-Met facilitate metastasis through the ERK signaling pathway in prostate cancer cells Corrigendum in /10.3892/or.2022.8388

Yin,Binbin; Liu,Zhenping; Wang,Yiyun; Wang,Xuchu; Liu,Weiwei; Yu,Pan; Duan,Xiuzhi; Liu,Chunhua; Chen,Yuhua; Zhang,Yurong; Pan,Xiaoyan; Yao,Hangping; Liao,Zhaoping; Tao,Zhihua

doi:10.3892/or.2017.5585

RON and c-Met facilitate metastasis through the ERK signaling pathway in prostate cancer cells

Corrigendum in: /10.3892/or.2022.8388

Authors:
- Binbin Yin
- Zhenping Liu
- Yiyun Wang
- Xuchu Wang
- Weiwei Liu
- Pan Yu
- Xiuzhi Duan
- Chunhua Liu
- Yuhua Chen
- Yurong Zhang
- Xiaoyan Pan
- Hangping Yao
- Zhaoping Liao
- Zhihua Tao
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Affiliations: Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China, Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China, Department of Blood Transfusion, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China, Key Laboratory of Laboratory Medicine, Chinese Ministry of Education, Zhejiang Provincial Key State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital of Zhejiang University School of Medicine Hangzhou, Hangzhou, Zhejiang, P.R. China
Published online on: April 19, 2017 https://doi.org/10.3892/or.2017.5585
Pages: 3209-3218
Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prostate cancer (PCa) is a metastatic malignant cancer driven by complex pathological mechanisms and characterized by poor long-term prognosis. Metastasis is the main cause of death of PCa patients, yet the molecular mechanisms of this process are poorly understood. In the present study, positive co-expression of RON and c-Met was observed in human clinical PCa tissues (biopsy material), as detected by immunohistochemical staining and quantitative real-time PCR. We investigated this further in PCa cells, demonstrating that the inhibition of RON and c-Met with foretinib (GSK1363089) suppressed metastasis and promoted the reversal of the epithelial-to-mesenchymal transition (EMT) in PCa cells. Furthermore, the invasion and migration of PCa cells were enhanced by the exogenous activation of RON with MSP and c-Met with HGF, whereas silencing of RON and c-Met attenuated the invasion and metastasis of the PCa cells. Our data also demonstrated that HGF/c-Met, but not the MSP-RON signaling pathway may be the dominant mechanism for PCa EMT. We further revealed that RON and c-Met facilitate metastasis via ERK1/2 signaling. These findings indicate that RON and c-Met facilitate metastasis through ERK1/2 signaling and that targeting RON and c-Met with foretinib may be an attractive therapeutic option for suppressing PCa metastasis.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA: A Cancer Journal for Clinicians. 65:5–29. 2015.PubMed/NCBI
2	Park JC and Eisenberger MA: Advances in the Treatment of Metastatic Prostate Cancer. Mayo Clin Proc. 90:1719–1733. 2015. View Article : Google Scholar : PubMed/NCBI
3	Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 5:871–90. 2009. View Article : Google Scholar
4	Park M, Dean M, Kaul K, Braun MJ, Gonda MA and Vande WG: Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors. Proc Natl Acad Sci U S A. 84:pp. 6379–83. 1987; View Article : Google Scholar : PubMed/NCBI
5	Chang K, Karnad A, Zhao S and Freeman JW: Roles of c-Met and RON kinases in tumor progression and their potential as therapeutic targets. Oncotarget. 6:3507–18. 2015. View Article : Google Scholar : PubMed/NCBI
6	Ronsin C, Muscatelli F, Mattei MG and Breathnach R: A novel putative receptor protein tyrosine kinase of the met family. Oncogene. 8:1195–202. 1993.PubMed/NCBI
7	Birchmeier C, Birchmeier W, Gherardi E and Woude GF Vande: Met, metastasis, motility and more. Nat Rev Mol Cell Bio. 4:915–925. 2003. View Article : Google Scholar
8	Wang J, Rajput A, Kan JLC, Rose R, Liu XQ, Kuropatwinski K, Hauser J, Beko A, Dominquez I, Sharratt EA, Brattain L, LeVea C, Sun FL, Keane DM, Gibson NW and Brattain MG: Knockdown of Ron Kinase Inhibits Mutant Phosphatidylinositol 3-Kinase and Reduces Metastasis in Human Colon Carcinoma. J Biol Chem. 284:10912–10922. 2009. View Article : Google Scholar : PubMed/NCBI
9	Lee WY, Chen HH, Chow NH, Su WC, Lin PW and Guo HR: Prognostic significance of co-expression of RON and MET receptors in node-negative breast cancer patients. Clin Cancer Res. 11:2222–8. 2005. View Article : Google Scholar : PubMed/NCBI
10	Faria CC, Golbourn BJ, Dubuc AM, Remke M, Diaz RJ, Agnihotri S, Luck A, Sabha N, Olsen S, Wu X, Garzia L, Ramaswamy V, Mack SC, Wang X, Leadley M, Reynaud D, Ermini L, Post M, Northcott PA, Pfister SM, Croul SE, Kool M, Korshunov A, Smith CA, Taylor MD and Rutka JT: Foretinib Is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma. Cancer Res. 75:134–146. 2015. View Article : Google Scholar : PubMed/NCBI
11	Kataoka Y, Mukohara T, Tomioka H, Funakoshi Y, Kiyota N, Fujiwara Y, Yashiro M, Hirakawa K, Hirai M and Minami H: Foretinib (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, inhibits growth of gastric cancer cell lines by blocking inter-receptor tyrosine kinase networks. Invest New Drugs. 30:1352–60. 2012. View Article : Google Scholar : PubMed/NCBI
12	Huynh H, Ong R and Soo KC: Foretinib demonstrates anti-tumor activity and improves overall survival in preclinical models of hepatocellular carcinoma. Angiogenesis. 15:59–70. 2012. View Article : Google Scholar : PubMed/NCBI
13	You WK, Sennino B, Williamson CW, Falcon B, Hashizume H, Yao LC, Aftab DT and McDonald DM: VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res. 71:4758–68. 2011. View Article : Google Scholar : PubMed/NCBI
14	Huynh H, Ong R and Soo KC: Foretinib demonstrates anti-tumor activity and improves overall survival in preclinical models of hepatocellular carcinoma. Angiogenesis. 15:59–70. 2012. View Article : Google Scholar : PubMed/NCBI
15	Shah MA, Wainberg ZA, Catenacci DV, Hochster HS, Ford J, Kunz P, Lee FC, Kallender H, Cecchi F, Rabe DC, Keer H, Martin AM, Liu Y, Gagnon R, Bonate P, Liu L, Gilmer T and Bottaro DP: Phase II study evaluating 2 dosing schedules of oral foretinib (GSK1363089), cMET/VEGFR2 inhibitor, in patients with metastatic gastric cancer. Plos One. 8:e540142013. View Article : Google Scholar : PubMed/NCBI
16	Choueiri TK, Vaishampayan U, Rosenberg JE, Logan TF, Harzstark AL, Bukowski RM, Rini BI, Srinivas S, Stein MN, Adams LM, Ottesen LH, Laubscher KH, Sherman L, McDermott DF, Haas NB, Flaherty KT, Ross R, Eisenberg P, Meltzer PS, Merino MJ, Bottaro DP, Linehan WM and Srinivasan R: Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma. J Clin Oncol. 31:181–6. 2013. View Article : Google Scholar : PubMed/NCBI
17	Seiwert T, Sarantopoulos J, Kallender H, McCallum S, Keer HN and Blumenschein G: Phase II trial of single-agent foretinib (GSK1363089) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Invest New Drug. 2:417–24. 2012.
18	Yau T, Yen CJ, Chen PJ, Chau Y, Lencioni R, Kallender H, Ottesen LH and Poon RTP: A phase I/II study of foretinib, an oral multikinase inhibitor targeting MET RON, AXL, TIE-2, and VEGFR in advanced hepatocellular carcinoma (HCC). J Hepatol. 54:S2682011. View Article : Google Scholar
19	Knubel KH, Pernu BM, Sufit A, Nelson S, Pierce AM and Keating AK: MerTK inhibition is a novel therapeutic approach for glioblastoma multiforme. Oncotarget. 5:1338–51. 2014. View Article : Google Scholar : PubMed/NCBI
20	Shtutman M, Levina E, Ohouo P, Baig M and Roninson IB: Cell Adhesion Molecule L1 Disrupts E-Cadherin-Containing Adherens Junctions and Increases Scattering and Motility of MCF7 Breast Carcinoma Cells. Cancer Res. 66:11370–11380. 2006. View Article : Google Scholar : PubMed/NCBI
21	Yao H, Zhou Y, Zhang R and Wang M: MSP-RON signalling in cancer: pathogenesis and therapeutic potential. Nat Rev Cancer. 13:466–481. 2013. View Article : Google Scholar : PubMed/NCBI
22	Kretschmann KL, Eyob H, Buys SS and Welm AL: The macrophage stimulating protein/Ron pathway as a potential therapeutic target to impede multiple mechanisms involved in breast cancer progression. Curr Drug Targets. 11:1157–68. 2010. View Article : Google Scholar : PubMed/NCBI
23	Lee WY, Chen HH, Chow NH, Su WC, Lin PW and Guo HR: Prognostic significance of co-expression of RON and MET receptors in node-negative breast cancer patients. Clin Cancer Res. 11:2222–8. 2005. View Article : Google Scholar : PubMed/NCBI
24	Follenzi A, Bakovic S, Gual P, Stella MC, Longati P and Comoglio PM: Cross-talk between the proto-oncogenes Met and Ron. Oncogene. 19:3041–9. 2000. View Article : Google Scholar : PubMed/NCBI
25	Benvenuti S, Lazzari L, Arnesano A, Li CG, Gentile A and Comoglio PM: Ron kinase transphosphorylation sustains MET oncogene addiction. Cancer Res. 71:1945–55. 2011. View Article : Google Scholar : PubMed/NCBI
26	Wang D, Shen Q, Chen YQ and Wang MH: Collaborative activities of macrophage-stimulating protein and transforming growth factor-beta1 in induction of epithelial to mesenchymal transition: roles of the RON receptor tyrosine kinase. Oncogene. 23:1668–80. 2004. View Article : Google Scholar : PubMed/NCBI
27	Ma Q, Guin S, Padhye SS, Zhou YQ, Zhang RW and Wang MH: Ribosomal protein S6 kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein. Mol Cancer. 10:662011. View Article : Google Scholar : PubMed/NCBI