RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer

Song, Young-A; Park, Young‐Lan; Kim, Kyu-Yeol; Myung, Eun; Chung, Chul; Cho, Sung-Bum; Lee, Wan‐Sik; Jung, Yoon Young; Kweon, Sun-Seog; Joo, Young‐Eun

doi:10.1111/j.1440-1827.2011.02765.x

Cited by 21 publications

(23 citation statements)

References 37 publications

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“…Our results suggested that the knockdown of RON inhibited cell proliferation (Figure 3A,C), cell migration (Figure 5A,B), and cell invasion (Figure 6A,B) in AGS and MKN-28 cells. Song et al previously reported that RON is associated with cell cycle arrest in gastric cancer cells [44]. In this study, knockdown of RON also markedly induced G1 arrest in AGS cells (Figure 4B).…”

Section: Resultssupporting

confidence: 73%

MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais

Lian

Xia

Nguyen

et al. 2016

IJMS

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Emerging evidence supports a fundamental role for microRNAs (miRNA) in regulating cancer metastasis. Recently, microRNA-375 (miR-375) was reported to be downregulated in many types of cancers, including gastric cancer. Increase in the expression of Recepteur d’Origine Nantais (RON), a receptor tyrosine kinase, has been reported in tumors. However, the function of miR-375 and RON expression in gastric cancer metastasis has not been sufficiently studied. In silico analysis identified miR-375 binding sites in the 3′-untranslated regions (3′-UTR) of the RON-encoding gene. Expression of miR-375 resulted in reduced activity of a luciferase reporter containing the 3′-UTR fragments of RON-encoding mRNA, confirming that miR-375 directly targets the 3′-UTR of RON mRNA. Moreover, we found that overexpression of miR-375 inhibited mRNA and protein expression of RON, which was accompanied by the suppression of cell proliferation, migration, and invasion in gastric cancer AGS and MKN-28 cells. Ectopic miR-375 expression also induced G1 cell cycle arrest through a decrease in the expression of cyclin D1, cyclin D3, and in the phosphorylation of retinoblastoma (Rb). Knockdown of RON by RNAi, similar to miR-375 overexpression, suppressed tumorigenic properties and induced G1 arrest through a decrease in the expression of cyclin D1, cyclin D3, and in the phosphorylation of Rb. Thus, our study provides evidence that miR-375 acts as a suppressor of metastasis in gastric cancer by targeting RON, and might represent a new potential therapeutic target for gastric cancer.

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Section: Resultssupporting

confidence: 73%

MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais

Lian

Xia

Nguyen

et al. 2016

IJMS

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“…Several studies have suggested that RON is associated with apoptosis in various cancer cells (42,43). However, the impact of RON on apoptosis in human bladder cancer is not reported.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis

Chen

et al. 2017

Oncology Reports

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Epirubicin (EPI) is one of the most used intravesical chemotherapy agents after transurethral resection to non-muscle invasive bladder tumors (NMIBC) to prevent cancer recurrence and progression. However, even after resection of bladder tumors and intravesical chemotherapy, half of them will recur and progress. RON is a membrane tyrosine kinase receptor usually overexpressed in bladder cancer cells and associated with poor pathological features. This study aims to investigate the effects of anti-RON monoclonal antibody Zt/g4 on the chemosensitivity of bladder cells to EPI. After Zt/g4 treatment, cell cytotoxicity was significantly increased and cell invasion was markedly suppressed in EPI-treated bladder cancer cells. Further investigation indicated that combing Zt/g4 with EPI promoted cell G1/S-phase arrest and apoptosis, which are the potential mechanisms that RON signaling inhibition enhances chemosensitivity of EPI. Thus, combing antibody-based RON targeted therapy enhances the therapeutic effects of intravesical chemotherapy, which provides new strategy for further improvement of NMIBC patient outcomes.

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“…RON signaling has been shown to promote apoptotic resistance in multiple preclinical cancer models, including thyroid, gastric, and colon cancer 18,19,70 . In the context of pancreatic cancer, subcutaneous L3.6pl-induced tumors treated with a RON monoclonal antibody resulted in a 1.3-fold increase in apoptosis compared with the control group, assessed by TUNEL staining (p<0.03) 51 .…”

Section: Apoptotic Resistancementioning

confidence: 99%

The RON Receptor Tyrosine Kinase in Pancreatic Cancer Pathogenesis and Its Potential Implications for Future Targeted Therapies

Kang¹,

Babicky²,

Lowy³

2014

Pancreas

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Pancreatic cancer remains a devastating disease with a mortality rate that has not changed substantially in decades. Novel therapies are therefore desperately needed. The RON receptor tyrosine kinase has been identified as an important mediator of KRAS oncogene addiction and is over-expressed in the majority of pancreatic cancers. Preclinical studies that inhibition of RON function decrease pancreatic cancer cell migration, invasion and survival and can sensitize pancreatic cancer cells to chemotherapy. This article reviews the current state of knowledge regarding RON biology and pancreatic cancer and discusses its potential as a therapeutic target.

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RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer

Cited by 21 publications

References 37 publications

MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais

MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais

Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis

The RON Receptor Tyrosine Kinase in Pancreatic Cancer Pathogenesis and Its Potential Implications for Future Targeted Therapies

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