Short-form RON (sf-RON) enhances glucose metabolism to promote cell proliferation via activating beta-catenin/SIX1 signaling pathway in gastric cancer

摘要

Recepteur d'origine nantais (RON) has been implicated in cell proliferation, metastasis, and chemoresistance of various human malignancies. The short-form RON (sf-RON) encoded by RON transcripts was overexpressed in gastric cancer tissues, but its regulatory functions remain illustrated. Here, we found that sf-RON promoted gastric cancer cell proliferation by enhancing glucose metabolism. Furthermore, sf-RON was proved to induce the beta-catenin expression level through the AKT1/GSK3 beta signaling pathway. Meanwhile, the binding sites of beta-catenin were identified in the promoter region of SIX1 and it was also demonstrated that beta-catenin positively regulated SIX1 expression. SIX1 enhanced the promoter activity of key proteins in glucose metabolism, such as GLUT1 and LDHA. Results indicated that sf-RON regulated the cell proliferation and glucose metabolism of gastric cancer by participating in a sf-RON/beta-catenin/SIX1 signaling axis and had significant implications for choosing the therapeutic target of gastric cancer.