HIGD1A Regulates Oxygen Consumption, ROS Production, and AMPK Activity during Glucose Deprivation to Modulate Cell Survival and Tumor Growth
| Autor: | Timothy A. Sanders, Matthew L. Wheeler, Anthony M. Rajah, Ravi Nagarajan, Stefanie S. Jeffrey, Emin Maltepe, Michael P. Murphy, Paolo Rinaudo, Arman Jahangiri, Kathryn V. Tormos, Melike Pekmezci, Yerem Yeghiazarians, Joseph F. Costello, Manish K. Aghi, Kurosh Ameri, Vien Nguyen |
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| Rok vydání: | 2014 |
| Předmět: |
1.1 Normal biological development and functioning
Medical Physiology chemistry.chemical_element Biology Oxygen General Biochemistry Genetics and Molecular Biology law.invention Underpinning research law Genetics 2.1 Biological and endogenous factors Aetiology lcsh:QH301-705.5 Gene HIGD1A Cancer Chromosome Promoter Cell biology Glucose deprivation lcsh:Biology (General) chemistry Suppressor Dormancy Generic health relevance Biochemistry and Cell Biology |
| Zdroj: | Ameri, K; Jahangiri, A; Rajah, AM; Tormos, KV; Nagarajan, R; Pekmezci, M; et al.(2015). HIGD1A Regulates Oxygen Consumption, ROS Production, and AMPK Activity during Glucose Deprivation to Modulate Cell Survival and Tumor Growth. Cell Reports, 10(6), 891-899. doi: 10.1016/j.celrep.2015.01.020. UCSF: Retrieved from: http://www.escholarship.org/uc/item/5dg2z36c Cell reports, vol 10, iss 6 Cell Reports, Vol 10, Iss 6, Pp 891-899 (2015) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2015.01.020. |
| Popis: | © 2015 The Authors. Hypoxia-inducible gene domain family member 1A (HIGD1A) is a survival factor induced by hypoxia-inducible factor 1 (HIF-1). HIF-1 regulates many responses to oxygen deprivation, but viable cells within hypoxic perinecrotic solid tumor regions frequently lack HIF-1α. HIGD1A is induced in these HIF-deficient extreme environments and interacts with the mitochondrial electron transport chain to repress oxygen consumption, enhance AMPK activity, and lower cellular ROS levels. Importantly, HIGD1A decreases tumor growth but promotes tumor cell survival invivo. The human Higd1a gene is located on chromosome 3p22.1, where many tumor suppressor genes reside. Consistent with this, the Higd1a gene promoter is differentially methylated in human cancers, preventing its hypoxic induction. However, when hypoxic tumor cells are confronted with glucose deprivation, DNA methyltransferase activity is inhibited, enabling HIGD1A expression, metabolic adaptation, and possible dormancy induction. Our findings therefore reveal important new roles for this family of mitochondrial proteins in cancer biology. |
| Databáze: | OpenAIRE |
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