Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis
TLDR
Findings support a novel role for pyruvate in metabolic signaling and suggest a mechanism by which high rates of aerobic glycolysis can promote the malignant transformation and survival of cancer cells.About:
This article is published in Journal of Biological Chemistry.The article was published on 2002-06-28 and is currently open access. It has received 773 citations till now. The article focuses on the topics: Warburg effect & Anaerobic glycolysis.read more
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Why do cancers have high aerobic glycolysis
TL;DR: In this article, the authors propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions, which leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity.
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Cancer Cell Metabolism: Warburg and Beyond
TL;DR: The Warburg effect of aerobic glycolysis is re-examine and a framework for understanding its contribution to the altered metabolism of cancer cells is established.
Journal ArticleDOI
Functional polarization of tumour-associated macrophages by tumour-derived lactic acid
Oscar R. Colegio,Ngoc Quynh Chu,Alison L. Szabo,Thach Chu,Anne Marie Rhebergen,Vikram Jairam,Nika Cyrus,Carolyn Brokowski,Stephanie C. Eisenbarth,Gillian M. Phillips,Gary W. Cline,Andrew J. Phillips,Ruslan Medzhitov +12 more
TL;DR: It is shown that lactic acid produced by tumour cells, as a by-product of aerobic or anaerobic glycolysis, has a critical function in signalling, through inducing the expression of vascular endothelial growth factor and the M2-like polarization of tumour-associated macrophages and this effect is mediated by hypoxia-inducible factor 1α (HIF1α).
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Redox Regulation of Cell Survival
Dunyaporn Trachootham,Dunyaporn Trachootham,Dunyaporn Trachootham,Weiqin Lu,Marcia A. Ogasawara,Nilsa Rivera-Del Valle,Nilsa Rivera-Del Valle,Peng Huang +7 more
TL;DR: The current understanding of how disturbance in redox homeostasis may affect cell death and contribute to the development of diseases such as cancer and degenerative disorders is reviewed and the basic knowledge on redox regulation of cell survival can be used to develop strategies for the treatment or prevention of those diseases.
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Hypoxia-inducible factor-1 (HIF-1).
Qingdong Ke,Max Costa +1 more
TL;DR: Overexpression of HIF-1 has been found in various cancers, and targeting Hif-1 could represent a novel approach to cancer therapy.
References
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Targeting of HIF-alpha to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation
Panu Jaakkola,David R. Mole,Ya-Min Tian,Michael I. Wilson,Janine Gielbert,Simon J. Gaskell,Alex von Kriegsheim,Holger F. Hebestreit,Mridul Mukherji,Christopher J. Schofield,Patrick H. Maxwell,Christopher W. Pugh,Peter J. Ratcliffe +12 more
TL;DR: It is shown that the interaction between human pVHL and a specific domain of the HIF-1α subunit is regulated through hydroxylation of a proline residue by an enzyme the authors have termed Hif-α prolyl-hydroxylase (HIF-PH).
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HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing
Mircea Ivan,Keiichi Kondo,Haifeng Yang,William Y. Kim,Jennifer Valiando,Michael Ohh,Adrian Salic,John M. Asara,William S. Lane,William G. Kaelin,William G. Kaelin +10 more
TL;DR: It is found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated, which may play a key role in mammalian oxygen sensing.