Coordinate regulation of stress signaling and epigenetic events by Acss2 and HIF-2 in cancer cells

Rui Chen, Min Xu, Jason Nagati, Joseph A. Garcia

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Survival of cancer cells in the harsh tumor microenvironment, characterized by oxygen and glucose deprivation, requires rapid initiation of cytoprotective measures. Metabolites whose levels change during stress are ideal signaling cues, particularly if used in post-translational modifications of stress-responsive signal transducers. In cancer cells exposed to oxygen or glucose deprivation, there is an increase in cellular levels of acetate, a substrate for acetate-dependent acetyl CoA synthetase 2 (Acss2) that also stimulates translocation of Acss2 from the cytosol to the nucleus. Nuclear, but not cytosolic, Acss2 promotes acetylation of the stress-responsive Hypoxia Inducible Factor 2α (HIF-2α) subunit by the acetyltransferase/ coactivator Creb binding protein (Cbp), a process that facilitates stable Cbp/HIF-2α complex formation. In addition to promoting de novo transcription, Cbp and HIF-2α act in concert to regulate local histone 3 epigenetic marks. Exogenous acetate augments Acss2/HIF-2 dependent cancer growth and metastasis in cell culture and mouse models. Thus, an acetate switch in mammals links nutrient intake and stress signaling with tumor growth and metastasis.

Original languageEnglish (US)
Article numbere0190241
JournalPLoS One
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

acetate-CoA ligase
Acetate-CoA Ligase
Epigenomics
epigenetics
hypoxia
Acetates
acetates
Cells
binding proteins
Carrier Proteins
metastasis
neoplasms
Tumors
Neoplasms
Oxygen
Neoplasm Metastasis
oxygen
Glucose
Acetylation
glucose

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Coordinate regulation of stress signaling and epigenetic events by Acss2 and HIF-2 in cancer cells. / Chen, Rui; Xu, Min; Nagati, Jason; Garcia, Joseph A.

In: PLoS One, Vol. 12, No. 12, e0190241, 01.12.2017.

Research output: Contribution to journalArticle

Chen, Rui ; Xu, Min ; Nagati, Jason ; Garcia, Joseph A. / Coordinate regulation of stress signaling and epigenetic events by Acss2 and HIF-2 in cancer cells. In: PLoS One. 2017 ; Vol. 12, No. 12.
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