Mouse models to elucidate mechanisms of folate-related cancer pathologies

Abstract

Perturbations in folate metabolism are associated with risk for colon cancer, although the underlying mecha-nisms remain to be established. It is not known if the associations between disruptions in folate metabolism and cancer result from altered S-adenosylmethionine (SAM; also known/abbreviated as AdoMet) synthesis and/or deoxythymidylic acid (dTMP) synthesis. Cyto-plasmic serine hydroxymethyltransferase (cSHMT) is a metabolic switch that directs the partitioning of folate-activated one-carbon units between dTMP and SAM bio-synthesis. cSHMT is expressed in tissues associated with folate-related pathologies, including the colon. Therefore, gain-of-function and loss-of-function cSHMT mouse models can be used to elucidate the contributions of the dTMP and SAM biosynthetic pathways to colon cancer