Mutant ras elevates dependence on serum lipids and creates a synthetic lethality for rapamycin.

ABSTRACT: The conversion of normal cells to cancer cells involves a shift from catabolic to anabolic metabolism involving increased glucose uptake and the diversion of glycolytic intermediates into nucleotides, amino acids, and lipids needed for cell growth. An underappreciated aspect of nutrient uptake is the utilization of serum lipids. We investigated the dependence of human cancer cells on serum lipids and report here that Ras-driven human cancer cells are uniquely dependent on serum lipids for both proliferation and survival. Removal of serum lipids also sensitizes Ras-driven cancer cells to rapamycin-indicating that the enhanced need for serum lipids creates a synthetic lethal phenotype that could be exploited therapeutically. Although depriving humans of serum lipids is not practical, suppres

SUBMITTER: Salloum D 

PROVIDER: S-EPMC4001122 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature