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

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 fo...

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Bibliographic Details
Published in:Cell biology and toxicology 2021-02, Vol.37 (1), p.35-49
Main Authors: Wang, Ziliang, Yang, Yufei, Hu, Shuang, He, Jian, Wu, Zheng, Qi, Zihao, Huang, Mingzhu, Liu, Rujiao, Lin, Ying, Tan, Cong, Xu, Midie, Zhang, Zhe
Format: Article
Language:English
Subjects:
AKT1 protein
Animals
Base Sequence
beta Catenin - metabolism
Binding sites
Biochemistry
Biomedical and Life Sciences
Cancer
Cell Biology
Cell growth
Cell Line, Tumor
Cell Proliferation
Chemoresistance
Disease Progression
Gastric cancer
Glucose
Glucose - metabolism
Glycolysis
Homeodomain Proteins - metabolism
Humans
Life Sciences
Male
Metabolism
Metastases
Mice
Mice, Inbred BALB C
Mice, Nude
Original
Original Article
Pharmacology/Toxicology
Receptor Protein-Tyrosine Kinases - metabolism
Ron protein
Signal Transduction
Signaling
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Survival Analysis
β-Catenin
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Summary: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.
ISSN:0742-2091
1573-6822
DOI:10.1007/s10565-020-09525-5