Related Experiment Video For BCAT2
Updated: Jul 11, 2025

Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
Deficiency of BCAT2-mediated branched-chain amino acid catabolism promotes colorectal cancer development
Zi-Ran Kang1, Shanshan Jiang1, Ji-Xuan Han1
1Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Objective:
Branched-chain amino acid (BCAA) metabolism is involved in the development of colorectal cancer (CRC); however, the underlying mechanism remains unclear. Therefore, this study investigates the role of BCAA metabolism in CRC progression.
Methods:
Dietary BCAA was administered to both azoxymethane-induced and azoxymethane/dextran sodium sulfate-induced CRC mouse models. The expression of genes related to BCAA metabolism was determined using RNA sequencing. Adjacent tissue samples, obtained from 58 patients with CRC, were subjected to quantitative real-time PCR and immunohistochemical analysis. Moreover, the suppressive role of branched-chain aminotransferase 2 (BCAT2) in cell proliferation, apoptosis, and xenograft mouse models was investigated. Alterations in BCAAs and activation of downstream pathways were also assessed using metabolic analysis and western blotting.
Results:
High levels of dietary BCAA intake promoted CRC tumorigenesis in chemical-induced CRC and xenograft mouse models. Both the mRNA and protein levels of BCAT2 were decreased in tumor tissues of patients with CRC compared to those in normal tissues. Proliferation assays and xenograft models confirmed the suppressive role of BCAT2 in CRC progression. Furthermore, the accumulation of BCAAs caused by BCAT2 deficiency facilitated the chronic activation of mTORC1, thereby mediating the oncogenic effect of BCAAs.
Conclusion:
BCAT2 deficiency promotes CRC progression through inhibition of BCAAs metabolism and chronic activation of mTORC1.
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