Acss2/HIF-2 signaling facilitates colon cancer growth and metastasis
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)...
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| Veröffentlicht in: | PloS one 2023-03, Vol.18 (3), p.e0282223-e0282223 |
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| creator | Garcia, Joseph A Chen, Rui Xu, Min Comerford, Sarah A Hammer, Robert E Melton, Shelby D Feagins, Linda A |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0282223 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0282223</identifier><identifier>PMID: 36862715</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetate-CoA Ligase ; Acetates ; Acetic acid ; Animals ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Biology and Life Sciences ; Biotechnology ; Cancer ; Cell culture ; Cell migration ; Cellular signal transduction ; Colon cancer ; Colonic Neoplasms ; Colorectal cancer ; Cyclic AMP response element-binding protein ; Deprivation ; Development and progression ; Dextrose ; Enzymes ; Epithelial cells ; Epithelium ; Fibrosarcoma ; Genetic aspects ; Glucose ; Growth ; Health aspects ; Humans ; Hypoxia ; Medicine and Health Sciences ; Metastases ; Metastasis ; Mice ; Microenvironments ; Oncology, Experimental ; Oxygen ; Physical Sciences ; Protein binding ; Proteins ; Research and analysis methods ; Sarcoma ; Signal Transduction ; Signaling ; SIRT1 protein ; Solid tumors ; Synergistic effect ; Transcription factors ; Tumor cell lines ; Tumor Microenvironment ; Tumors ; Work stations</subject><ispartof>PloS one, 2023-03, Vol.18 (3), p.e0282223-e0282223</ispartof><rights>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. 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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. 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Targeted inhibition of Acss2/HIF-2 signaling may have synergistic effects for some colon cancer patients.</description><subject>Acetate-CoA Ligase</subject><subject>Acetates</subject><subject>Acetic acid</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Biology and Life Sciences</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cell migration</subject><subject>Cellular signal transduction</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms</subject><subject>Colorectal cancer</subject><subject>Cyclic AMP response element-binding protein</subject><subject>Deprivation</subject><subject>Development and progression</subject><subject>Dextrose</subject><subject>Enzymes</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Fibrosarcoma</subject><subject>Genetic 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>36862715</pmid><doi>10.1371/journal.pone.0282223</doi><tpages>e0282223</tpages><orcidid>https://orcid.org/0000-0002-5621-7538</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| subjects | Acetate-CoA Ligase Acetates Acetic acid Animals Basic Helix-Loop-Helix Transcription Factors - genetics Biology and Life Sciences Biotechnology Cancer Cell culture Cell migration Cellular signal transduction Colon cancer Colonic Neoplasms Colorectal cancer Cyclic AMP response element-binding protein Deprivation Development and progression Dextrose Enzymes Epithelial cells Epithelium Fibrosarcoma Genetic aspects Glucose Growth Health aspects Humans Hypoxia Medicine and Health Sciences Metastases Metastasis Mice Microenvironments Oncology, Experimental Oxygen Physical Sciences Protein binding Proteins Research and analysis methods Sarcoma Signal Transduction Signaling SIRT1 protein Solid tumors Synergistic effect Transcription factors Tumor cell lines Tumor Microenvironment Tumors Work stations |
| title | Acss2/HIF-2 signaling facilitates colon cancer growth and metastasis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T10%3A18%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Acss2/HIF-2%20signaling%20facilitates%20colon%20cancer%20growth%20and%20metastasis&rft.jtitle=PloS%20one&rft.au=Garcia,%20Joseph%20A&rft.date=2023-03-02&rft.volume=18&rft.issue=3&rft.spage=e0282223&rft.epage=e0282223&rft.pages=e0282223-e0282223&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0282223&rft_dat=%3Cgale_plos_%3EA739277949%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2781563827&rft_id=info:pmid/36862715&rft_galeid=A739277949&rft_doaj_id=oai_doaj_org_article_21dcbf5e7af9419d9861f6c9ebcf5d72&rfr_iscdi=true |