BCAT1 decreases the sensitivity of cancer cells to cisplatin by regulating mTOR-mediated autophagy via branched-chain amino acid metabolism.

ABSTRACT: Cisplatin is one of the most effective chemotherapy drugs and is widely used in the treatment of cancer, including hepatocellular carcinoma (HCC) and cervical cancer, but its therapeutic benefit is limited by the development of resistance. Our previous studies demonstrated that BCAT1 promoted cell proliferation and decreased cisplatin sensitivity in HCC cells. However, the exact role and mechanism of how BCAT1 is involved in cisplatin cytotoxicity remain undefined. In this study, we revealed that cisplatin triggered autophagy in cancer cells, with an increase in BCAT1 expression. The cisplatin-induced up-regulation of BCAT1 decreased the cisplatin sensitivity by regulating autophagy through the mTOR signaling pathway. In addition, branched-chain amino acids or leucine treatment inhibited c

SUBMITTER: Luo L 

PROVIDER: S-EPMC7876012 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature