title: Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function.
abstract: Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. BCAA catabolism is a conserved regulator of physiological aging and participates in diverse physiological and pathological processes, including carcinoma development. The roles of BCAA catabolism in human breast cancer remains unknown. Here we provide evidence that BCAA catabolism is involved in human breast cancer. The plasma and tissue levels of BCAAs are increased in breast cancer, which is accompanied by the elevated expression of the catabolic enzymes, including branched-chain amino acid transaminase 1 (BCAT1). Knockdown of BCAT1 represses the growth rate and colony formation capacity of breast cancer cells, opposing results are observed when BCAT1 is overexpressed. BCAT1 can promote mitochondrial biogenesis, ATP production and repress mitochondrial ROS in breast cancer cells by regulating the expression of related genes. Mechanism study reveals that BCAT1 activates the mTOR, but not AMPK or SIRT1, signaling to promote mitochondrial biogenesis and function, and subsequently facilitates growth and colony formation of breast cancer cells. Taken together, we demonstrate that BCAA catabolism is activated in human breast cancer, and abolishment of BCAA catabolism by knocking down BCAT1 inhibits breast cancer cell growth by repressing mTOR-mediated mitochondrial biogenesis and function.
authors.affiliation: Department of Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province 250000, China; Department of Clinical Oncology, Taian City Central Hospital, Taian, Shandong Province 271000, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province 250000, China. Electronic address: junqing_han@sina.com.
authors.forename: Junqing
authors.initials: J
authors.lastname: Han
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria / Q000378:metabolism; D001678:Organelle Biogenesis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D000637:Transaminases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; C490590:BCAT1 protein, human; D000637:Transaminases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: BCAT1; Branched-chain amino acid; Breast cancer; Mitochondrial biogenesis; mTOR