BioProject

Cancer cells alter their metabolism for the production of precursors of macromolecules. More...

Cancer cells alter their metabolism for the production of precursors of macromolecules. However, the control mechanisms underlying this reprogramming are poorly understood. Here, we show that metabolic reprogramming of colorectal cancer is caused chiefly by aberrant MYC expression. Multi-omics-based analyses of paired normal and tumor tissues from 275 patients with colorectal cancer revealed that metabolic alterations occur at the adenoma stage of carcinogenesis, in a manner not associated with specific gene mutations involved in colorectal carcinogenesis. MYC expression induced at least 215 metabolic reactions by changing the expression levels of 121 metabolic genes and 39 transporter genes. Further, MYC negatively regulated the expression of genes involved in mitochondrial biogenesis and maintenance but positively regulated genes involved in DNA and histone methylation. Knockdown of MYC in colorectal cancer cells reset the altered metabolism and suppressed cell growth. Moreover, inhibition of MYC target pyrimidine synthesis genes such as CAD, UMPS and CTPS blocked cell growth, and thus they are potential targets for colorectal cancer therapy. Overall design: Gene expression in HCT116 cells transfected with control or MYC siRNAs was measured. Four independent experiments were performed at each siRNA. Less...