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

ABSTRACT: 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 ?-catenin expression level through the AKT1/GSK3? signaling pathway. Meanwhile, the binding sites of ?-catenin were identified in the promoter region of SIX1 and it was also demonstrated that ?-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/?-catenin/SIX1 signaling axis and had significant implications for choosing the therapeutic target of gastric cancer.

SUBMITTER: Wang Z 

PROVIDER: S-EPMC7851020 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature