Glucose-independent acetate metabolism promotes melanoma cell survival and tumor growth

Alexander J. Lakhter, James Hamilton, Raymond Konger, Nikolai Broustovetski, Hal Broxmeyer, Samisubbu Naidu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Tumors rely on multiple nutrients to meet cellular bioenergetics and macromolecular synthesis demands of rapidly dividing cells. Although the role of glucose and glutamine in cancer metabolism is well understood, the relative contribution of acetate metabolism remains to be clarified. We show that glutamine supplementation is not sufficient to prevent loss of cell viability in a subset of glucose-deprived melanoma cells, but synergizes with acetate to support cell survival. Glucose-deprived melanoma cells depend on both oxidative phosphorylation and acetate metabolism for cell survival. Acetate supplementation significantly contributed to maintenance of ATP levels in glucose-starved cells. Unlike acetate, short chain fatty acids such as butyrate and propionate failed to prevent loss of cell viability from glucose deprivation. In vivo studies revealed that in addition to nucleo-cytoplasmic acetate assimilating enzyme ACSS2, mitochondrial ACSS1 was critical for melanoma tumor growth in mice. Our data indicate that acetate metabolism may be a potential therapeutic target for BRAF mutant melanoma.

Original languageEnglish (US)
Pages (from-to)21869-21879
Number of pages11
JournalJournal of Biological Chemistry
Volume291
Issue number42
DOIs
StatePublished - Oct 14 2016

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Metabolism
Tumors
Melanoma
Cell Survival
Acetates
Cells
Glucose
Growth
Neoplasms
Glutamine
Volatile Fatty Acids
Butyrates
Oxidative Phosphorylation
Propionates
Energy Metabolism
Nutrients
Adenosine Triphosphate
Maintenance
Food
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Glucose-independent acetate metabolism promotes melanoma cell survival and tumor growth. / Lakhter, Alexander J.; Hamilton, James; Konger, Raymond; Broustovetski, Nikolai; Broxmeyer, Hal; Naidu, Samisubbu.

In: Journal of Biological Chemistry, Vol. 291, No. 42, 14.10.2016, p. 21869-21879.

Research output: Contribution to journalArticle

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