Approximately 10 - 20% of gastric cancer presented an increased MET gene copy numbers; inappropriate activation of MET promotes cellular proliferation, cell motility, invasiveness and angiogenesis and is associated with more aggressive phenotype and with a lower survival.
Overall, our results indicate that prolonged MAPK pathway inhibition could result in acquired resistance which is associated with increased malignant phenotype in KRAS mutant GC and pharmacological targeting c-MET and PI3K/mTOR could overcome this problem.
In the present study, we identified three frequently amplified genes from 30 candidate genes using real-time quantitative PCR method, including ERBB4, C-MET and CD44, and further explored their association with clinicopathological characteristics and poor survival in a cohort of gastric cancers.
In 123 cases with primary and corresponding local recurrent/distant metastatic GC, 3 (2.4%) showed MET positivity in which 2 (66.7%) were discordant (positive conversion).
Patients with HER2(+) /EGFR(+) /MET(+) GCs had a substantial risk of death with a hazard ratio of 3.01 (95% CI: 1.54-5.90), compared with HER2(-) /EGFR(-) /MET(-) GC patients.
A multivariate analysis suggested that MET positivity may still be prognostic for worse median overall survival in gastric cancer; therefore, it is important to continue investigation into the optimal approach to inhibit MET signaling in gastric cancer.
We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis.
Similar results were obtained in additional GC cell lines with amplification of MET or the FGF receptor FGFR2 MKN45 murine xenograft experiments demonstrated the antitumor activity of M-COPA in vivo Taken together, our results offer an initial preclinical proof of concept for the use of M-COPA as a candidate treatment option for MET-addicted GC, with broader implications for targeting the Golgi apparatus as a novel cancer therapeutic approach.
MACC1, a transcriptional regulator of MET, was recognized as an oncogene in gastric cancer (GC); however, its transcriptional or post-translational regulation was not clear.
This study aimed to explore the molecular segmentation of several known therapeutics targets, human epidermal growth factor receptor 2 (HER2), MET and fibroblast growth factor receptor 2 (FGFR2), within GC using clinically approved or investigational kits and scoring criteria.
Importance of the type I insulin-like growth factor receptor in HER2, FGFR2 and MET-unamplified gastric cancer with and without Ras pathway activation.
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood.
This study describes the prevalence and prognostic value of EGFR and c-MET in a Canadian population of patients undergoing curative intent resection for GC.
These results overall suggest that amplification of the c-met gene might participate in carcinogenesis and progression of stomach cancer, especially scirrhous type stomach carcinoma.