Journal ArticleDOI
HIFs and tumors--causes and consequences.
TLDR
In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.Abstract:
For most organisms oxygen is essential for life. When oxygen levels drop below those required to maintain the minimum physiological oxygen requirement of an organism or tissue it is termed hypoxia. To counteract possible deleterious effects of such a state, an immediate molecular response is initiated causing adaptation responses aimed at cell survival. This response is mediated by the hypoxia-inducible factor-1 (HIF-1), which is a heterodimer consisting of an α- and a β-subunit. HIF-1α protein is stabilized under hypoxic conditions and therefore confers selectivity to this response. Hypoxia is characteristic of tumors, mainly because of impaired blood supply resulting from abnormal growth. Over the past few years enormous progress has been made in the attempt to understand how the activation of the physiological response to hypoxia influences neoplastic growth. In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.read more
Citations
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Adipokines: inflammation and the pleiotropic role of white adipose tissue.
Paul Trayhurn,I. Stuart Wood +1 more
TL;DR: It is suggested that the term ‘adipokine’ be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue.
Journal ArticleDOI
Hypoxia and Adipose Tissue Function and Dysfunction in Obesity
TL;DR: Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity.
Journal ArticleDOI
Signalling role of adipose tissue: adipokines and inflammation in obesity.
Paul Trayhurn,I S Wood +1 more
TL;DR: The elevated production of inflammation-related adipokines is increasingly considered to be important in the development of diseases linked to obesity, particularly Type II diabetes and the metabolic syndrome.
Journal ArticleDOI
The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance
TL;DR: In this review, it is discussed how enlarged adipocytes, an impaired blood flow through adipose tissue, adipOSE tissue hypoxia, adiposes tissue inflammation and macrophage infiltration are interrelated and may induce insulin resistance.
Journal ArticleDOI
Endocrine and signalling role of adipose tissue: new perspectives on fat.
TL;DR: From the wide range of adipokines now identified, it is evident that WAT is highly integrated into overall physiological regulation, involving extensive crosstalk with other organs and multiple metabolic systems.
References
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Journal ArticleDOI
Angiogenesis in cancer and other diseases
Peter Carmeliet,Rakesh K. Jain +1 more
TL;DR: Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases and integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases, but owing to several unanswered questions, caution is needed.
Journal ArticleDOI
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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The phosphatidylinositol 3-Kinase AKT pathway in human cancer.
Igor Vivanco,Charles L. Sawyers +1 more
TL;DR: Small-molecule therapeutics that block PI3K signalling might deal a severe blow to cancer cells by blocking many aspects of the tumour-cell phenotype.
Journal ArticleDOI
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).
Journal ArticleDOI
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.
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