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Acss2/HIF-2 signaling facilitates colon cancer growth and metastasis.

Authors :
Garcia JA
Chen R
Xu M
Comerford SA
Hammer RE
Melton SD
Feagins LA
Source :
PloS one [PLoS One] 2023 Mar 02; Vol. 18 (3), pp. e0282223. Date of Electronic Publication: 2023 Mar 02 (Print Publication: 2023).
Publication Year :
2023

Abstract

The microenvironment of solid tumors is characterized by oxygen and glucose deprivation. Acss2/HIF-2 signaling coordinates essential genetic regulators including acetate-dependent acetyl CoA synthetase 2 (Acss2), Creb binding protein (Cbp), Sirtuin 1 (Sirt1), and Hypoxia Inducible Factor 2α (HIF-2α). We previously shown in mice that exogenous acetate augments growth and metastasis of flank tumors derived from fibrosarcoma-derived HT1080 cells in an Acss2/HIF-2 dependent manner. Colonic epithelial cells are exposed to the highest acetate levels in the body. We reasoned that colon cancer cells, like fibrosarcoma cells, may respond to acetate in a pro-growth manner. In this study, we examine the role of Acss2/HIF-2 signaling in colon cancer. We find that Acss2/HIF-2 signaling is activated by oxygen or glucose deprivation in two human colon cancer-derived cell lines, HCT116 and HT29, and is crucial for colony formation, migration, and invasion in cell culture studies. Flank tumors derived from HCT116 and HT29 cells exhibit augmented growth in mice when supplemented with exogenous acetate in an Acss2/HIF-2 dependent manner. Finally, Acss2 in human colon cancer samples is most frequently localized in the nucleus, consistent with it having a signaling role. Targeted inhibition of Acss2/HIF-2 signaling may have synergistic effects for some colon cancer patients.<br />Competing Interests: The authors have declared that no competing interests exist.<br /> (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Details

Language :
English
ISSN :
1932-6203
Volume :
18
Issue :
3
Database :
MEDLINE
Journal :
PloS one
Publication Type :
Academic Journal
Accession number :
36862715
Full Text :
https://doi.org/10.1371/journal.pone.0282223