Scavenging of extracellular protein via macropinocytosis is an alternative to monomeric amino acid uptake. In pancreatic cancer, macropinocytosis is driven by oncogenic Ras signaling and contributes substantially to amino acid supply. While Ras signaling promotes scavenging, mTOR signaling suppresses it. Here, we present an integrated experimental-computational method that enables quantitative comparison of protein scavenging rates across cell lines and conditions. Using it, we find that, independently of mTORC1, amino acid scarcity induces protein scavenging and that under such conditions the impact of mTOR signaling on protein scavenging rate is minimal. Nevertheless, mTOR inhibition promotes growth of cells reliant on eating extracellular protein. This growth enhancement depends on mTORC1's canonical function in controlling translation rate: mTOR inhibition slows translation, thereby matching protein synthesis to the limited amino acid supply. Thus, paradoxically, in amino acid-poor conditions the pro-anabolic effects of mTORC1 are functionally opposed to growth.
Pubmed ID: 28918901 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets 4E-BP1
View all literature mentionsThis monoclonal targets Vinculin
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets CHOP (D46F1) Rabbit mAb
View all literature mentionsThis monoclonal targets ATF-4
View all literature mentionsThis monoclonal targets 4E-BP1, phospho (Thr37 / Thr46)
View all literature mentionsThis monoclonal targets Phospho-S6 Ribosomal Protein (Ser240/244) (D68F8) XP Rabbit mAb
View all literature mentionsThis monoclonal targets p70 S6 Kinase
View all literature mentionsThis polyclonal targets Phospho-p70 S6 Kinase (Thr389)
View all literature mentions