EGFR-Pak Signaling Selectively Regulates Glutamine Deprivation-Induced Macropinocytosis.

ABSTRACT: Macropinocytosis has emerged as an important nutrient-scavenging pathway that supports tumor cell fitness. By internalizing extracellular protein and targeting it for lysosomal degradation, this endocytic pathway functions as an amino acid supply route, permitting tumor cell growth and survival despite the nutrient-poor conditions of the tumor microenvironment. Here, we provide evidence that a subset of pancreatic ductal adenocarcinoma (PDAC) tumors are wired to integrate contextual metabolic inputs to regulate macropinocytosis, dialing up or down this uptake pathway depending on nutrient availability. We find that regional depletion of amino acids coincides with increased levels of macropinocytosis and that the scarcity of glutamine uniquely drives this process. Mechanistically, this stim

SUBMITTER: Lee SW 

PROVIDER: S-EPMC6684838 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature