AMPK inhibits Smad3-mediated autoinduction of TGF-β1 in gastric cancer cells.

ABSTRACT: We have previously shown that adenine monophosphate-activated protein kinase (AMPK) regulates transforming growth factor β (TGF-β)-triggered Smad3 phosphorylation. Here we report that AMPK inhibits TGF-β1 production. First, metformin reduced mRNA levels of TGF-β1 in gastric cancer cells, in parallel to the decrease of its protein abundance. The effects were more prominent in the cells containing LKB1, an upstream kinase of AMPK. Second, knockdown of Smad3 by siRNA abrogated the expression of TGF-β1. Third, metformin suppressed firefly luciferase activity whose transcription was driven by TGF-β1 promoter. In accordance, deletion of the putative binding site of Smad3 in the TGF-β1 promoter region severely impaired the promoter activity and response to metformin. Fourth, in support of our in

SUBMITTER: Zou J 

PROVIDER: S-EPMC7957200 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature