Abstract
Abstract Colon cancer is a common malignancy and its poor outcome mainly attributes to chemotherapy resistance. AMP-activated protein kinase (AMPK) is noted to mediate development of and chemotherapy resistance in colon cancer. This study aims to explore the mechanism regarding AMPK-mediated β-catenin degradation in chemotherapy resistance in colon cancer. β-catenin was upregulated in colon cancer tissues and cells, as it was positively correlated with the malignancy and poor prognosis, and chemotherapy resistance of colon cancer. As colon cancer cells were exposed to cisplatin and tamoxifen, functional experiment revealed that AMPK activated by its agonist metformin inhibited the proliferation and chemotherapy resistance of colon cancer cells by regulating β-catenin. Co-immunoprecipitation assay confirmed the interaction between β-catenin, E3 ubiquitin ligase Parkin and AMPK. Finally, we xenografted tumors in nude mice and validated the effects of AMPK and β-catenin on tumor growth and chemotherapy resistance in vivo. Parkin induced ubiquitination and degradation of β-catenin while AMPK downregulated β-catenin by elevating the phosphorylation of Parkin. Taken together, AMPK phosphorylates Parkin to promote the ubiquitination and degradation of β-catenin, thereby downregulating β-catenin, which inhibits the proliferation of colon cancer cells and reverses the chemotherapy resistance in colon cancer.
Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
