Fig. 2

BCAA hypocatabolism promotes tumour development. Leucine affects mTORC activity by regulating the ubiquitination state of Sestrin2. BCAA accumulation promotes the progression of hepatocellular carcinoma, colorectal cancer, non-small cell lung cancer, and leukaemia by activating the mTORC signalling pathway. EZH2, MSI2 and NARS^G12D are involved in regulating the expression of BCAT1, which leads to an increase in the catabolic reverse reaction of BCAAs and then promotes the activation of mTORC. The downregulation of BCAT2, BCKDHA and BCKDHB led to a reduction in BCAA catabolism and promotes the activation of mTORC. Deletion of PPM1K leads to BCAA accumulation by increasing the ubiquitination of MEIS1 and p21, damaging the dry nature of HSCs and LICs and leading to leukaemia. In addition, BCAA accumulation promotes ROS production through the PI3K/AKT signalling pathway, leading to mitochondrial dysfunction. BCAA accumulation caused by the overexpression of BCKDK may protect NSCLC cells by maintaining glycolysis and reducing ROS accumulation