Glutamate and asparagine cataplerosis underlie glutamine addiction in melanoma

Oncotarget
Boris RatnikovDavid A Scott

Abstract

Glutamine dependence is a prominent feature of cancer metabolism, and here we show that melanoma cells, irrespective of their oncogenic background, depend on glutamine for growth. A quantitative audit of how carbon from glutamine is used showed that TCA-cycle-derived glutamate is, in most melanoma cells, the major glutamine-derived cataplerotic output and product of glutaminolysis. In the absence of glutamine, TCA cycle metabolites were liable to depletion through aminotransferase-mediated α-ketoglutarate-to-glutamate conversion and glutamate secretion. Aspartate was an essential cataplerotic output, as melanoma cells demonstrated a limited capacity to salvage external aspartate. Also, the absence of asparagine increased the glutamine requirement, pointing to vulnerability in the aspartate-asparagine biosynthetic pathway within melanoma metabolism. In contrast to melanoma cells, melanocytes could grow in the absence of glutamine. Melanocytes use more glutamine for protein synthesis rather than secreting it as glutamate and are less prone to loss of glutamate and TCA cycle metabolites when starved of glutamine.

References

Mar 15, 1979·The Biochemical Journal·M WatfordH A Krebs
Oct 1, 1985·Quarterly Journal of Experimental Physiology : an International Journal of the Physiological Society·E A NewsholmeM S Ardawi
May 12, 1998·Cellular and Molecular Life Sciences : CMLS·F Massière, M A Badet-Denisot
Jun 28, 2002·The Journal of Biological Chemistry·Oliver E OwenRichard W Hanson
Sep 13, 2005·The Journal of Surgical Research·Bryan C Fuchs, Barrie P Bode
Oct 19, 2006·Bioinformatics·Boyke BunkKarsten Hiller
Jul 4, 2007·The Journal of Cell Biology·Mariia YunevaYuri Lazebnik
Nov 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ralph J DeBerardinisCraig B Thompson
Oct 17, 2008·Breast Cancer Research : BCR·Joshua Marshall ThornburgJason Chesney
Nov 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·David R WiseCraig B Thompson
Jan 30, 2009·Cell Cycle·Dmitri WiederschainJohn D Benson
Aug 19, 2011·Molecular Systems Biology·Daniela GaglioFerdinando Chiaradonna
Oct 15, 2011·The Journal of Biological Chemistry·David A ScottJeffrey W Smith
Nov 22, 2011·Nature·Christian M MetalloGregory Stephanopoulos
Nov 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·David R WiseCraig B Thompson
Aug 18, 2012·Metabolic Engineering·Taylor A MurphyJamey D Young
Oct 2, 2012·PloS One·Jessica De IngeniisJeffrey W Smith
Nov 17, 2012·Cancer Cell·Guoliang QingM Celeste Simon
Feb 27, 2013·Clinics in Dermatology·Ragini R KudchadkarVernon K Sondak
Dec 7, 2013·Cancer & Metabolism·Shawn McGuirkJulie St-Pierre
Jun 15, 2014·American Journal of Clinical Dermatology·Chante KarimkhaniRobert P Dellavalle

❮ Previous
Next ❯

Citations

Jan 30, 2018·ELife·Sara CalhounAndrej Sali
Apr 21, 2018·Scientific Reports·Christine WasingerMartin Hohenegger
Aug 30, 2020·International Journal of Molecular Sciences·Stefan Bröer
Jun 9, 2016·Oncogene·B I RatnikovZ A Ronai
Oct 30, 2019·International Journal of Molecular Medicine·Ningchuan SunHaitao Niu
Sep 26, 2019·World Journal of Microbiology & Biotechnology·Angela Beckett, David Gervais
Jun 9, 2020·The Journal of Experimental Medicine·Maria Victoria RecouvreuxCosimo Commisso
Sep 25, 2017·International Journal of Cancer. Journal International Du Cancer·Stefan Rodic, Mark David Vincent
Sep 27, 2018·The Biochemical Journal·Diego Avellaneda MatteoChristal D Sohl
Mar 10, 2019·Scientific Reports·Paul CastellanoEliseo A Eugenin
Nov 20, 2019·Nature Cell Biology·Gaurav PathriaZe'ev A Ronai
May 22, 2019·The Journal of Clinical Investigation·Lu-Lin JiangHuaxi Xu
Jun 21, 2018·Biological Chemistry·Monica Vara-PerezPatrizia Agostinis
Jul 20, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Laura RemachaAlberto Cascón
Feb 27, 2021·Molecular Cancer Therapeutics·Yongmei FengZe'ev A Ronai
May 5, 2021·The Journal of Clinical Investigation·William GiblinDavid B Lombard

❮ Previous
Next ❯

Methods Mentioned

BETA
deamidation
deamination
Assay
transfections
transfection
scraping

Software Mentioned

Metaquant

Related Concepts

Related Feeds

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.

Related Papers

The Journal of Immunology : Official Journal of the American Association of Immunologists
M D Prager, I Derr
The Journal of Biological Chemistry
G C WEBSTER, J E VARNER
Proceedings of the National Academy of Sciences of the United States of America
David R WiseCraig B Thompson
Neurochemistry International
Grethe M Olsen, Ursula Sonnewald
© 2022 Meta ULC. All rights reserved