Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer
Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of the...
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| Format: | Article |
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Elsevier
2018
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| Online Access: | http://hdl.handle.net/1721.1/116557 https://orcid.org/0000-0002-4236-0229 https://orcid.org/0000-0002-5410-6543 https://orcid.org/0000-0003-0130-3428 https://orcid.org/0000-0002-6745-8222 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0002-6702-4192 |
| _version_ | 1811096890629947392 |
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| author | Papagiannakopoulos, Thales Olenchock, Benjamin A. Heyman, Julia E. Jha, Abhishek K. Pierce, Kerry A. Mott, Bryan T. Clish, Clary B. Davidson, Shawn M. Luengo, Alba Bauer, Matthew R. Keibler, Mark Andrew O'Brien, James P. Gui, Dan Yi Sullivan, Lucas Bryan Wasylenko, Thomas Michael Subbaraj, Lakshmipriya Chin, Christopher R. Stephanopolous, Gregory Jacks, Tyler E. Vander Heiden, Matthew G. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Papagiannakopoulos, Thales Olenchock, Benjamin A. Heyman, Julia E. Jha, Abhishek K. Pierce, Kerry A. Mott, Bryan T. Clish, Clary B. Davidson, Shawn M. Luengo, Alba Bauer, Matthew R. Keibler, Mark Andrew O'Brien, James P. Gui, Dan Yi Sullivan, Lucas Bryan Wasylenko, Thomas Michael Subbaraj, Lakshmipriya Chin, Christopher R. Stephanopolous, Gregory Jacks, Tyler E. Vander Heiden, Matthew G. |
| author_sort | Papagiannakopoulos, Thales |
| collection | MIT |
| description | Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells. |
| first_indexed | 2024-09-23T16:51:00Z |
| format | Article |
| id | mit-1721.1/116557 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:51:00Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1165572022-10-03T08:42:27Z Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer Papagiannakopoulos, Thales Olenchock, Benjamin A. Heyman, Julia E. Jha, Abhishek K. Pierce, Kerry A. Mott, Bryan T. Clish, Clary B. Davidson, Shawn M. Luengo, Alba Bauer, Matthew R. Keibler, Mark Andrew O'Brien, James P. Gui, Dan Yi Sullivan, Lucas Bryan Wasylenko, Thomas Michael Subbaraj, Lakshmipriya Chin, Christopher R. Stephanopolous, Gregory Jacks, Tyler E. Vander Heiden, Matthew G. Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Davidson, Shawn M. Luengo, Alba Bauer, Matthew R. Keibler, Mark Andrew O'Brien, James P. Gui, Dan Yi Sullivan, Lucas Bryan Wasylenko, Thomas Michael Subbaraj, Lakshmipriya Chin, Christopher R. Stephanopolous, Gregory Jacks, Tyler E. Vander Heiden, Matthew G. Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells. National Science Foundation (U.S.) (Grant T32GM007287) 2018-06-25T15:12:04Z 2018-06-25T15:12:04Z 2016-02 2015-11 2018-06-25T14:52:04Z Article http://purl.org/eprint/type/JournalArticle 1550-4131 1932-7420 http://hdl.handle.net/1721.1/116557 Davidson, Shawn M. et al. “Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer.” Cell Metabolism 23, 3 (March 2016): 517–528 © 2016 Elsevier Inc https://orcid.org/0000-0002-4236-0229 https://orcid.org/0000-0002-5410-6543 https://orcid.org/0000-0003-0130-3428 https://orcid.org/0000-0002-6745-8222 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0002-6702-4192 http://dx.doi.org/10.1016/J.CMET.2016.01.007 Cell Metabolism Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Papagiannakopoulos, Thales Olenchock, Benjamin A. Heyman, Julia E. Jha, Abhishek K. Pierce, Kerry A. Mott, Bryan T. Clish, Clary B. Davidson, Shawn M. Luengo, Alba Bauer, Matthew R. Keibler, Mark Andrew O'Brien, James P. Gui, Dan Yi Sullivan, Lucas Bryan Wasylenko, Thomas Michael Subbaraj, Lakshmipriya Chin, Christopher R. Stephanopolous, Gregory Jacks, Tyler E. Vander Heiden, Matthew G. Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer |
| title | Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer |
| title_full | Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer |
| title_fullStr | Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer |
| title_full_unstemmed | Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer |
| title_short | Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer |
| title_sort | environment impacts the metabolic dependencies of ras driven non small cell lung cancer |
| url | http://hdl.handle.net/1721.1/116557 https://orcid.org/0000-0002-4236-0229 https://orcid.org/0000-0002-5410-6543 https://orcid.org/0000-0003-0130-3428 https://orcid.org/0000-0002-6745-8222 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0002-6702-4192 |
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