Research progress on the development of hepatocyte growth factor/c-Met signaling pathway in gastric cancer: A review.

Hepatocyte growth factor (HGF) and its receptor, c-Met, play important roles in the occurrence, development, and treatment of gastric cancer (GC). This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic mechanisms. As one of the most common malignant tumors worldwide, GC has a complex pathogenesis and limited therapeutic options. Therefore, a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic methods. The HGF/c-Met signaling pathway plays an important role in the proliferation, migration, and invasion of GC cells and has become a new therapeutic target. This review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway, providing new ideas and directions for the treatment of GC.

Wei WJ ，Hong YL ，Deng Y ，Wang GL ，Qiu JT ，Pan F ... -  《World Journal of Gastrointestinal Oncology》

Current advances of targeting HGF/c-Met pathway in gastric cancer.

Anestis A ，Zoi I ，Karamouzis MV 《-》

SMYD3 Modulates the HGF/MET Signaling Pathway in Gastric Cancer.

De Marco K ，Lepore Signorile M ，Di Nicola E ，Sanese P ，Fasano C ，Forte G ，Disciglio V ，Pantaleo A ，Varchi G ，Del Rio A ，Grossi V ，Simone C ... -  《Cells》

Co-expression of hepatocyte growth factor and c-Met predicts peritoneal dissemination established by autocrine hepatocyte growth factor/c-Met signaling in gastric cancer.

Epithelial-mesenchymal transition (EMT) promotes and facilitates migration and invasion of epithelial tumor cells. EMT is induced by factors such as hepatocyte growth factor (HGF). This study aimed to establish whether the HGF/c-Met pathway is associated with gastric cancer metastasis; especially peritoneal dissemination. HGF and c-Met expression and EMT-related molecules were evaluated using real-time PCR and immunohistochemistry. The role of the HGF/c-Met pathway in EMT and anoikis was determined, and kinase inhibitor SU11274 was tested for its ability to block HGF-induced biological effects. In HGF(-) /c-Met(+) gastric cancer cells, recombinant HGF promoted an EMT phenotype that was characterized by morphology, impaired E-cadherin and induction of vimentin. HGF promoted cell growth, invasiveness and migration and inhibition of anoikis. SU11274 blocked HGF-induced EMT and biological effects in vitro. In HGF(+) /c-Met(+) gastric cancer cells, HGF did not affect the biological outcome of EMT and anoikis, but SU11274 exerted the same inhibitory effects as in HGF(-) /c-Met(+) cells. In vivo, HGF(+) /c-Met(+) gastric cancer cells only established peritoneal dissemination and SU11274 inhibited tumor growth. Clinically, HGF expression was significantly correlated with c-Met expression in gastric cancer. Increased HGF and c-Met had a significant association with poor prognosis and predicted peritoneal dissemination. We demonstrated that the HGF/c-Met pathway induces EMT and inhibition of anoikis in gastric cancer cells. Co-expression of HGF and c-Met has the potential to promote peritoneal dissemination in gastric cancer. Blockade of the autocrine HGF/c-Met pathway could be clinically useful for the treatment of peritoneal dissemination in gastric cancer.

Toiyama Y ，Yasuda H ，Saigusa S ，Matushita K ，Fujikawa H ，Tanaka K ，Mohri Y ，Inoue Y ，Goel A ，Kusunoki M ... -  《-》

Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment.

Rothenberger NJ ，Stabile LP 《Cancers》