Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells Journal Article


Authors: Commisso, C.; Davidson, S. M.; Soydaner-Azeloglu, R. G.; Parker, S. J.; Kamphorst, J. J.; Hackett, S.; Grabocka, E.; Nofal, M.; Drebin, J. A.; Thompson, C. B.; Rabinowitz, J. D.; Metallo, C. M.; Vander Heiden, M. G.; Bar-Sagi, D.
Article Title: Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
Abstract: Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and its contents are internalized into cells through large, heterogeneous vesicles known as macropinosomes. Oncogenic Ras proteins have been shown to stimulate macropinocytosis but the functional contribution of this uptake mechanism to the transformed phenotype remains unknown. Here we show that Ras-transformed cells use macropinocytosis to transport extracellular protein into the cell. The internalized protein undergoes proteolytic degradation, yielding amino acids including glutamine that can enter central carbon metabolism. Accordingly, the dependence of Ras-transformed cells on free extracellular glutamine for growth can be suppressed by the macropinocytic uptake of protein. Consistent with macropinocytosis representing an important route of nutrient uptake in tumours, its pharmacological inhibition compromises the growth of Ras-transformed pancreatic tumour xenografts. These results identify macropinocytosis as a mechanism by which cancer cells support their unique metabolic needs and point to the possible exploitation of this process in the design of anticancer therapies. © 2013 Macmillan Publishers Limited. All rights reserved.
Journal Title: Nature
Volume: 497
Issue: 7451
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2013-05-30
Start Page: 633
End Page: 637
Language: English
DOI: 10.1038/nature12138
PROVIDER: scopus
PUBMED: 23665962
PMCID: PMC3810415
DOI/URL:
Notes: --- - "Export Date: 1 July 2013" - "CODEN: NATUA" - "Source: Scopus"
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  1. Craig Bernie Thompson
    153 Thompson