Short-form RON (sf-RON) enhances glucose metabolism to promote cell proliferation via activating β-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 β-catenin expression level through the AKT1/GSK3β signaling pathway. Meanwhile, the binding sites of β-catenin were identified in the promoter region of SIX1 and it was also demonstrated that β-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/β-catenin/SIX1 signaling axis and had significant implications for choosing the therapeutic target of gastric cancer.

journal_name

Cell Biol Toxicol

authors

Wang Z,Yang Y,Hu S,He J,Wu Z,Qi Z,Huang M,Liu R,Lin Y,Tan C,Xu M,Zhang Z

doi

10.1007/s10565-020-09525-5

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

35-49

issue

1

eissn

0742-2091

issn

1573-6822

pii

10.1007/s10565-020-09525-5

journal_volume

37

pub_type

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