Cytosolic serine hydroxymethyltransferase controls lung adenocarcinoma cells migratory ability by modulating AMP kinase activity.

ABSTRACT: Nutrient utilization and reshaping of metabolism in cancer cells is a well-known driver of malignant transformation. Less clear is the influence of the local microenvironment on metastasis formation and choice of the final organ to invade. Here we show that the level of the amino acid serine in the cytosol affects the migratory properties of lung adenocarcinoma (LUAD) cells. Inhibition of serine or glycine uptake from the extracellular milieu, as well as knockdown of the cytosolic one-carbon metabolism enzyme serine hydroxymethyltransferase (SHMT1), abolishes migration. Using rescue experiments with a brain extracellular extract, and direct measurements, we demonstrate that cytosolic serine starvation controls cell movement by increasing reactive oxygen species formation and decreasing ATP

SUBMITTER: Bouzidi A 

PROVIDER: S-EPMC7691363 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature