EPDR1 promotes gastric cancer progression via STAT3-mediated fatty acid metabolic reprogramming

EPDR1通过STAT3介导的脂肪酸代谢重编程促进胃癌进展

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Abstract

EPDR1 has been shown to play critical regulatory roles in development of several types of cancer. Nevertheless, the role of EPDR1, a family of glycoproteins involved in cell-cell contact, to gastric cancer (GC) remain unknown. Here, we determined that EPDR1 is significantly upregulated in GC tissues and cell lines, and is associated with poor prognosis. In vitro and in vivo functional assays demonstrate that EPDR1 promotes the proliferation, migration, and invasion of GC cells. Mechanistically, EPDR1 regulates the expression level of CPT1A, thereby mediating metabolic reprogramming of the fatty acid oxidation pathway. Our RNA immunoprecipitation (RIP) experiments show that CPT1A interacts with STAT3 in GC cell lines, and that EPDR1 mediates the phosphorylation of STAT3 via CPT1A. Overall, our work elucidates that EPDR1 activates the JAK-STAT pathway through the regulation of CPT1A, leading to enhanced phosphorylation of STAT3 and promoting fatty acid oxidation levels in GC, thus facilitating the progression of gastric cancer and providing a potential therapeutic target for its treatment.

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