{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jin P"],"funding":["Basic and Applied Basic Research Foundation of Guangdong Province"],"pagination":["e16082"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9728056"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(12)"],"pubmed_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 F<sub>1</sub> F<sub>O</sub> -ATPase activity, which conferred mitochondrial OXPHOS and ATP production. This metabolic preferen"],"journal":["EMBO molecular medicine"],"pubmed_title":["Disrupting metformin adaptation of liver cancer cells by targeting the TOMM34/ATP5B axis."],"pmcid":["PMC9728056"],"funding_grant_id":["2019B030302012"],"pubmed_authors":["Jiang J","Zhou L","Huang C","Chen HN","Ding N","Xie N","Li L","Wei Y","Qin S","Zhang W","Zhang T","Huang Z","Zhang Z","Nice EC","Luo M","Gao W","Jin P","Li B","Peng L","Ming H"],"additional_accession":[]},"is_claimable":false,"name":"Disrupting metformin adaptation of liver cancer cells by targeting the TOMM34/ATP5B axis.","description":"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 F<sub>1</sub> F<sub>O</sub> -ATPase activity, which conferred mitochondrial OXPHOS and ATP production. This metabolic preferen","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-05-27T23:40:26.133Z","creation":"2024-11-13T21:51:13.773Z"},"accession":"S-EPMC9728056","cross_references":{"pubmed":["36321555"],"doi":["10.15252/emmm.202216082"]}}