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Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and its contents are internalized into cells via large, heterogeneous vesicles known as macropinosomes. Oncogenic Ras proteins have been shown to stimulate macropinocytosis but the functional contribution of this u...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810415/ https://www.ncbi.nlm.nih.gov/pubmed/23665962 http://dx.doi.org/10.1038/nature12138 |
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author | Commisso, Cosimo Davidson, Shawn M. Soydaner-Azeloglu, Rengin G. Parker, Seth J. Kamphorst, Jurre J. Hackett, Sean Grabocka, Elda Nofal, Michel Drebin, Jeffrey A. Thompson, Craig B. Rabinowitz, Joshua D. Metallo, Christian M. Heiden, Matthew G. Vander Bar-Sagi, Dafna |
author_facet | Commisso, Cosimo Davidson, Shawn M. Soydaner-Azeloglu, Rengin G. Parker, Seth J. Kamphorst, Jurre J. Hackett, Sean Grabocka, Elda Nofal, Michel Drebin, Jeffrey A. Thompson, Craig B. Rabinowitz, Joshua D. Metallo, Christian M. Heiden, Matthew G. Vander Bar-Sagi, Dafna |
author_sort | Commisso, Cosimo |
collection | PubMed |
description | Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and its contents are internalized into cells via 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(1-3). Here we show that Ras-transformed cells utilize 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 tumor nutrient uptake, its pharmacological inhibition compromised the growth of Ras-transformed pancreatic tumor 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 anti-cancer therapies. |
format | Online Article Text |
id | pubmed-3810415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-38104152013-11-30 Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells Commisso, Cosimo Davidson, Shawn M. Soydaner-Azeloglu, Rengin G. Parker, Seth J. Kamphorst, Jurre J. Hackett, Sean Grabocka, Elda Nofal, Michel Drebin, Jeffrey A. Thompson, Craig B. Rabinowitz, Joshua D. Metallo, Christian M. Heiden, Matthew G. Vander Bar-Sagi, Dafna Nature Article Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and its contents are internalized into cells via 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(1-3). Here we show that Ras-transformed cells utilize 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 tumor nutrient uptake, its pharmacological inhibition compromised the growth of Ras-transformed pancreatic tumor 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 anti-cancer therapies. 2013-05-12 2013-05-30 /pmc/articles/PMC3810415/ /pubmed/23665962 http://dx.doi.org/10.1038/nature12138 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Commisso, Cosimo Davidson, Shawn M. Soydaner-Azeloglu, Rengin G. Parker, Seth J. Kamphorst, Jurre J. Hackett, Sean Grabocka, Elda Nofal, Michel Drebin, Jeffrey A. Thompson, Craig B. Rabinowitz, Joshua D. Metallo, Christian M. Heiden, Matthew G. Vander Bar-Sagi, Dafna Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells |
title | Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells |
title_full | Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells |
title_fullStr | Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells |
title_full_unstemmed | Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells |
title_short | Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells |
title_sort | macropinocytosis of protein is an amino acid supply route in ras-transformed cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810415/ https://www.ncbi.nlm.nih.gov/pubmed/23665962 http://dx.doi.org/10.1038/nature12138 |
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