BCAT1

Official Full Name

branched chain amino acid transaminase 1

Organism

Homo sapiens

GeneID

586

Background

This gene encodes the cytosolic form of the enzyme branched-chain amino acid transaminase. This enzyme catalyzes the reversible transamination of branched-chain alpha-keto acids to branched-chain L-amino acids essential for cell growth. Two different clinical disorders have been attributed to a defect of branched-chain amino acid transamination: hypervalinemia and hyperleucine-isoleucinemia. As there is also a gene encoding a mitochondrial form of this enzyme, mutations in either gene may contribute to these disorders. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2010]

Synonyms

BCT1; PP18; BCATC; ECA39; MECA39; PNAS121;

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Detailed Information

Branched-chain amino acid transaminase 1 (BCAT1), also known as cytoplasmic branched-chain aminotransferase and ECA39, is located on chromosome 12p12.1. It encodes the cytoplasmic form of the branched chain amino acid transaminase that catalyzes the reversible transamination of branched alpha-keto acids to the branched L-amino acids necessary for cell growth. It has been previously suggested that abnormal expression of BCAT1, and concomitant defects in the transamination of branched-chain amino acids, results in hyperproline and hyperleucine-isoleucine, and may play an important role in the cell growth, proliferation and apoptosis of numerous tumor types.

BCAT1 and breast cancer

Breast cancer is the most common invasive cancer in women and the second leading cause of cancer death in women after lung cancer. Recent studies have found an increase in plasma and tissue levels of branched-chain amino acids (BCAAs) in breast cancer, which was accompanied by increased expression of the catabolic enzyme, including BCAT1. Knockdown of BCAT1 inhibited the growth rate and colony forming ability of breast cancer cells, and the opposite result was observed when BCAT1 was overexpressed. BCAT1 promotes mitochondrial biogenesis, Adenosine triphosphate (ATP) production and inhibition of mitochondrial ROS in breast cancer cells by regulating the expression of related genes. Mechanism studies have shown that BCAT1 activates mammalian target of rapamycin (mTOR), but not AMP-activated protein kinase (AMPK) or silent mating type information regulation 2 homolog-1 (SIRT1), signaling to promote mitochondrial biogenesis and function, and subsequently facilitates breast cancer cell growth and colony formation. In conclusion, BCAA catabolism has been shown to be activated in human breast cancer, and breast cancer cell growth can be inhibited by knocking down BCAT1 to eliminate BCAA catabolism.

BCAT1 and HCC

Hepatocellular carcinoma (HCC) is one of the most common malignancies and its incidence is increasing. Recently, studies have found that BCAT1 expression was significantly higher in HCC tissues compared to adjacent non-tumor tissues. In addition, immunohistochemical analysis indicated that the expression of BCAT1 was positively correlated with c-Myc. BCAT1 expression was shown to be down-regulated in c-Myc knockdown cells, and silencing of BCAT1 expression reduced invasion and migration of HCC cells. In addition, clinical analysis showed that the expression of BCAT1 in HCC tissues was significantly associated with tumor-lymph node-metastasis stage, tumor number and tumor differentiation, and BCAT1 was able to predict 5-year survival rate and free survival rate of disease-HCC patients. In conclusion, BCAT1 expression is up-regulated in HCC patients, and BCAT1 can be used as a potential molecular target for HCC diagnosis and treatment.

BCAT1 and GC

Gastric cancer (GC) is the fourth most common cancer in the world and the second leading cause of cancer-related mortality in humans. It was reported that the expression of BCAT1 in human GC was significantly increased. Furthermore, it can also be found that BCAT1 overexpression was associated with tumor node metastasis (TNM) stage, local invasion, Lauren type, tumor classification, lymph node metastasis, and presence of distant metastasis. Kaplan-Meier survival analysis showed that high BCAT1 expression predicted a significant decrease in overall survival, while multivariate Cox regression analysis showed that BCAT1 independently affected GC. In conclusion, up-regulation of BCAT1 indicated a poor survival rate of GC and can be used as a useful marker for predicting the prognosis of patients with GC.

BCAT1 and EOC

Epithelial ovarian cancer (EOC) accounts for 4% of all cancers in women and is the leading cause of death in gynecologic malignancies. Knockdown of BCAT1 expression in EOC cells resulted in a dramatic decrease in cell proliferation, migration and invasion and inhibition of cell cycle progression. BCAT1 silencing was associated with suppression of numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, and the induction of some tumor suppressor genes (TSGs). Furthermore, BCAT1 inhibition led to down-regulation of many genes involved in lipid production and protein synthesis, indicating its important role in controlling EOC metabolism. Further metabolomics analysis indicated significant consumption of most amino acids and different phosphates and sphingolipids after BCAT1 knockdown. Finally, BCAT1 inhibition resulted in significantly prolonged survival time in xenograft models of advanced peritoneal EOC. In summary, the results provide new insights into the functional role of BCAT1 in ovarian carcinogenesis and identify this transaminase as a new EOC biomarker and a putative EOC therapeutic target.

In summary, current studies indicate that up-regulation of BCAT1 is associated with poor prognosis in many types of tumors. Therefore, further study of the mechanism of BCAT1 occurrence and development in tumors will provide important clinical pathological significance for the treatment of tumors.

References:

Meng X, et al. BCAT1 promotes tumor cell migration and invasion in hepatocellular carcinoma. Oncology Letters, 2016, 12: 2648-2656
Oktyabri D, et al. DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines. Biochimie, 2016, 123: 20-31
Zhang L, et al. Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function. Biochemical and Biophysical Research Communications, 2017, 486: 2
Zheng YH, et al. BCAT1, a key prognostic predictor of hepatocellular carcinoma, promotes cell proliferation and induces chemoresistance to cisplatin. Liver International, 36(12): 1836-1847
Xu Y, et al. Overexpression of BCAT1 is a prognostic marker in gastric cancer. Human Pathology, 2018, 75: 41-46
Wang ZQ, et al. BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism. Oncotarget, 2015, 6: 31

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