Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours.

ABSTRACT: As oxygen is essential for many metabolic pathways, tumour hypoxia may impair cancer cell proliferation^1-4. However, the limiting metabolites for proliferation under hypoxia and in tumours are unknown. Here, we assessed proliferation of a collection of cancer cells following inhibition of the mitochondrial electron transport chain (ETC), a major metabolic pathway requiring molecular oxygen⁵. Sensitivity to ETC inhibition varied across cell lines, and subsequent metabolomic analysis uncovered aspartate availability as a major determinant of sensitivity. Cell lines least sensitive to ETC inhibition maintain aspartate levels by importing it through an aspartate/glutamate transporter, SLC1A3. Genetic or pharmacologic modulation of SLC1A3 activity markedly altered cancer c

SUBMITTER: Garcia-Bermudez J 

PROVIDER: S-EPMC6030478 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature