Journal ArticleDOI
Oncogenic alterations of metabolism.
Chi V. Dang,Gregg L. Semenza +1 more
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Over seven decades of classical biochemical studies showed that tumors have altered metabolic profiles and display high rates of glucose uptake and glycolysis, which might confer a common advantage on many different types of cancers, which allows the cells to survive and invade.About:
This article is published in Trends in Biochemical Sciences.The article was published on 1999-02-01. It has received 1088 citations till now.read more
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Hypoxia — a key regulatory factor in tumour growth
TL;DR: Cells undergo a variety of biological responses when placed in hypoxic conditions, including activation of signalling pathways that regulate proliferation, angiogenesis and death, and many elements of the hypoxia-response pathway are good candidates for therapeutic targeting.
Journal ArticleDOI
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Patrick H. Maxwell,Michael S. Wiesener,Gin-Wen Chang,Steven C. Clifford,Emma C. Vaux,Matthew Edward Cockman,Charles C. Wykoff,Christopher W. Pugh,Eamonn R. Maher,Peter J. Ratcliffe,Peter J. Ratcliffe +10 more
TL;DR: It is indicated that the interaction between HIF-1 and pVHL is iron dependent, and that it is necessary for the oxygen-dependent degradation of HIF α-subunits, which may underlie the angiogenic phenotype of VHL-associated tumours.
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HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia
TL;DR: A hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production is revealed.
Journal ArticleDOI
Reactive oxygen species in cancer
Geou Yarh Liou,Peter Storz +1 more
TL;DR: The generation of ROS within tumour cells, their detoxification, their cellular effects, as well as the major signalling cascades they utilize are discussed, but also an outlook on their modulation in therapeutics is provided.
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Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects.
Michael Höckel,Peter Vaupel +1 more
TL;DR: Because malignant tumors no longer execute functions necessary for homeostasis (such as the production of adequate amounts of adenosine triphosphate), the physiology-based definitions of the term "hypoxia" are not necessarily valid for malignant tumor patients.
References
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Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis
TL;DR: The work from the authors' laboratories reviewed herein was supported by grants from the National Cancer Institute.
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Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension
TL;DR: Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells.
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Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1α
Narayan V. Iyer,Lori E. Kotch,Faton Agani,Sandra W. Leung,Erik Laughner,Roland H. Wenger,Max Gassmann,John D. Gearhart,Ann M. Lawler,Aimee Y. Yu,Gregg L. Semenza +10 more
TL;DR: It is demonstrated that HIF-1alpha is a master regulator of cellular and developmental O2 homeostasis in Hif1a-/- embryos that manifested neural tube defects, cardiovascular malformations, and marked cell death within the cephalic mesenchyme.
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Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.
Peter Carmeliet,Yuval Dor,Jean-Marc Herbert,Dai Fukumura,Koen Brusselmans,Mieke Dewerchin,Michal Neeman,Françoise Bono,Rinat Abramovitch,Patrick H. Maxwell,Cameron J. Koch,Peter J. Ratcliffe,Lieve Moons,Rakesh K. Jain,Desire Collen,Eli Keshert +15 more
TL;DR: It is shown that hypoxia and hypoglycaemia reduce proliferation and increase apoptosis in wild-type (Hif-1α+/+) embryonic stem (ES) cells, but not in ES cells with inactivated HIF-1 α genes (HIF- 1α−/−), suggesting that there are at least two different adaptive responses to being deprived of oxygen and nutrients.
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Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
Thomas G. Graeber,Cynthia Osmanian,Tyler Jacks,David E. Housman,Cameron J. Koch,Scott W. Lowe,Scott W. Lowe,Amato J. Giaccia +7 more
TL;DR: It is proposed that hypoxia provides a physiological selective pressure in tumours for the expansion of variants that have lost their apoptotic potential, and in particular for cells acquiring p53mutations.