Exogenous and Endogenous Sources of Serine Contribute to Colon Cancer Metabolism and Growth

Serine is a non-essential amino acid that is generated by the sequential actions of phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT1) and phosphoserine phosphatase (PSPH). Increased serine biosynthesis occurs in several cancers and supports tumor growth. In addition to serine synthesis, exogenous serine is taken up by cells and can also fuel tumor growth. Interestingly, colon cancer cells increase expression of serine biosynthesis enzymes in the absence of exogenous serine, suggesting a compensatory adaptive response to reduced availability of serine. This study explored the relative contributions of exogenous and synthesized serine to colon cancer cell growth, metabolism and response to anti-cancer therapy. Human colorectal cancer cells containing empty vector were cultured in control or serine deficient media and PSAT1 knockout cells were cultured in serine deficient medium for 24 hours and RNA seq analysis was carried out.