Disrupting metformin adaptation of liver cancer cells by targeting the TOMM34/ATP5B axis.

ABSTRACT: Metformin, a well-known antidiabetic drug, has been repurposed for cancer treatment; however, recently observed drug resistance and tumor metastasis have questioned its further application. Here, we found that long-term metformin exposure led to metabolic adaptation of hepatocellular carcinoma (HCC) cells, which was characterized by an obvious epithelial-mesenchymal transition (EMT) phenotype and compensatory elevation of oxidative phosphorylation (OXPHOS). TOMM34, a translocase of the outer mitochondrial membrane, was upregulated to promote tumor metastasis in response to metformin-induced metabolic stress. Mechanistically, TOMM34 interacted with ATP5B to preserve F₁ F_O -ATPase activity, which conferred mitochondrial OXPHOS and ATP production. This metabolic preferen

SUBMITTER: Jin P 

PROVIDER: S-EPMC9728056 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature