Carrot and stick: HIF-alpha engages c-Myc in hypoxic adaptation
- PMID: 18188166
- DOI: 10.1038/sj.cdd.4402302
Carrot and stick: HIF-alpha engages c-Myc in hypoxic adaptation
Abstract
The past decade of research on hypoxic responses has provided a considerable understanding of how cells respond to hypoxic stress at the molecular level, thanks to the identification and molecular cloning of the hypoxia-inducible transcription factor, HIF-1alpha. Numerous target genes have since been identified to account for various aspects of the hypoxic response, including angiogenesis and glycolysis. Yet, fundamental questions remain regarding the mechanisms by which hypoxia controls cell proliferation, genetic instability, mitochondrial biogenesis, and oxidative respiration in cancer cells. Although the proto-oncoprotein c-Myc appears to be the diametrical opposite of HIF-1alpha in most of these processes, recent studies indicate that c-Myc is an integral part of the HIF-alpha-c-Myc molecular pathway in the hypoxic response. It has been shown that HIF-alpha engages with Myc by various mechanisms to achieve oxygen homeostasis for cell survival. This article focuses on the intricate roles of c-Myc in the hypoxic response, discusses various mechanisms controlling c-Myc activity by HIF-alpha for the regulation of hypoxia-responsive genes, and emphasizing the outcome of gene expression apparently dependent upon hypoxic conditions, cellular context, and gene promoter.
Similar articles
-
HIF-1alpha induces cell cycle arrest by functionally counteracting Myc.EMBO J. 2004 May 5;23(9):1949-56. doi: 10.1038/sj.emboj.7600196. Epub 2004 Apr 8. EMBO J. 2004. PMID: 15071503 Free PMC article.
-
Mild chronic hypoxia-induced HIF-2α interacts with c-MYC through competition with HIF-1α to induce hepatocellular carcinoma cell proliferation.Cell Oncol (Dordr). 2021 Oct;44(5):1151-1166. doi: 10.1007/s13402-021-00625-w. Epub 2021 Aug 2. Cell Oncol (Dordr). 2021. PMID: 34339013
-
Hypoxic suppression of the cell cycle gene CDC25A in tumor cells.Cell Cycle. 2007 Aug 1;6(15):1919-26. doi: 10.4161/cc.6.15.4515. Epub 2007 May 27. Cell Cycle. 2007. PMID: 17671423
-
Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways.Drug Resist Updat. 2011 Jun;14(3):191-201. doi: 10.1016/j.drup.2011.03.001. Epub 2011 Apr 3. Drug Resist Updat. 2011. PMID: 21466972 Review.
-
Energy regulation: HIF MXIes it up with the C-MYC powerhouse.Dev Cell. 2007 Jun;12(6):845-6. doi: 10.1016/j.devcel.2007.05.006. Dev Cell. 2007. PMID: 17543856 Review.
Cited by
-
PFK15, a Small Molecule Inhibitor of PFKFB3, Induces Cell Cycle Arrest, Apoptosis and Inhibits Invasion in Gastric Cancer.PLoS One. 2016 Sep 26;11(9):e0163768. doi: 10.1371/journal.pone.0163768. eCollection 2016. PLoS One. 2016. PMID: 27669567 Free PMC article.
-
Mechanisms of the Metabolic Shift during Somatic Cell Reprogramming.Int J Mol Sci. 2019 May 7;20(9):2254. doi: 10.3390/ijms20092254. Int J Mol Sci. 2019. PMID: 31067778 Free PMC article. Review.
-
Oncogenic regulation of tumor metabolic reprogramming.Oncotarget. 2016 Sep 20;7(38):62726-62753. doi: 10.18632/oncotarget.10911. Oncotarget. 2016. PMID: 28040803 Free PMC article. Review.
-
Anthracycline inhibits recruitment of hypoxia-inducible transcription factors and suppresses tumor cell migration and cardiac angiogenic response in the host.J Biol Chem. 2012 Oct 12;287(42):34866-34882. doi: 10.1074/jbc.M112.374587. Epub 2012 Aug 20. J Biol Chem. 2012. PMID: 22908232 Free PMC article.
-
Immunotherapy, targeted therapy, and their cross talks in hepatocellular carcinoma.Front Immunol. 2023 Dec 19;14:1285370. doi: 10.3389/fimmu.2023.1285370. eCollection 2023. Front Immunol. 2023. PMID: 38173713 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous
