Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function
Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function
复制标题
DOI：
10.1016/j.bbrc.2017.02.101
复制
发表时间：
2017-04-29
影响因子：
3.1
通讯作者：
Han, Junqing
中科院分区：
文献类型：
--
作者：
Zhang, Ling;Han, Junqing
支链氨基酸（BCAA）是重要的营养信号，具有直接和间接的影响。支链氨基酸催化剂是生理老化的保守调节剂，并参与多种生理和病理过程，包括癌症的发展。BCAA催化剂在人类乳腺癌中的作用仍然未知。在这里，我们提供的证据表明，支链氨基酸catalysts是参与人类乳腺癌。在乳腺癌中，BCAA的血浆和组织水平增加，这伴随着分解代谢酶的表达升高，包括支链氨基酸转氨酶1（BCAT 1）。BCAT 1的敲除抑制乳腺癌细胞的生长速率和集落形成能力，当BCAT 1过表达时观察到相反的结果。BCAT 1可通过调控相关基因的表达，促进乳腺癌细胞线粒体生物合成、ATP生成，抑制线粒体ROS。机制研究表明，BCAT1激活mTOR，而不是AMPK或SIRT1，信号传导促进线粒体生物合成和功能，随后促进乳腺癌细胞的生长和集落形成。总之，我们证明了BCAA催化剂在人类乳腺癌中被激活，并且通过敲低BCAT1来废除BCAA催化剂通过抑制mTOR介导的线粒体生物发生和功能来抑制乳腺癌细胞生长。(C)2017爱思唯尔公司All rights reserved.
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. (C) 2017 Elsevier Inc. All rights reserved.