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Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function
Ist Teil von
Biochemical and biophysical research communications, 2017-04, Vol.486 (2), p.224-231
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2017
Quelle
Elsevier ScienceDirect Journals
Beschreibungen/Notizen
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.
•BCAA metabolism is activated in human breast cancer.•BCAT1 regulates growth and colony formation of breast cancer cells.•BCAT1 promotes mitochondrial biogenesis and function.•mTOR contributes to the function of BCAT1.