Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis

  title={Role of HIF-1$\alpha$ in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis},
  author={Peter Carmeliet and Yuval Dor and Jean-M. Herbert and Dai Fukumura and Koen Brusselmans and Mieke Dewerchin and Michal Neeman and Françoise Bono and Rinat Abramovitch and Patrick H. Maxwell and Cameron J. Koch and Peter J. Ratcliffe and Lieve Moons and Rakesh K. Jain and D{\'e}sir{\'e} Jos{\'e} Collen and Eli Keshet},
As a result of deprivation of oxygen (hypoxia) and nutrients, the growth and viability of cells is reduced. Hypoxia-inducible factor(HIF)-1α helps to restore oxygen homeostasis by inducing glycolysis, erythropoiesis and angiogenesis. Here we show 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-1α genes (HIF-1α−/−); however, a deficiency of HIF-1α does not affect apoptosis… 

The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis

Understanding the regulation of apoptosis during hypoxia and the mechanisms of resistance to apoptosis might lead to more specific treatments for solid tumours.

Hypoxia-Inducible Factor-1 (HIF-1)

Overexpression of HIF-1 has been found in various cancers, and targeting Hif-1 could represent a novel approach to cancer therapy.

HIF-1α and HIF-2α Differently Regulate the Radiation Sensitivity of NSCLC Cells

In HIF1 knockout cells, HIF-2α was strongly induced by hypoxia compared to wild type but the reverse was not seen in HIF2 knockout cells; and a strong radiosensitizing of H IF1, but not of Hif2, which was associated with a reduced extracellular pH and reduced glycolysis.

Hypoxia-Inducible Factor (HIF)-1 Regulatory Pathway and its Potential for Therapeutic Intervention in Malignancy and Ischemia

The HIF-1 pathway has the potential to be a therapeutic intervention for the treatment of diseases such as cancer and ischemia but requires significant improvement and modification before becoming commercially available.

Hypoxia-Inducible Factor 1α Is Essential for Cell Cycle Arrest during Hypoxia

It is shown that hypoxia causes a HIF-1α-dependent increase in the expression of the cyclin-dependent kinase inhibitors p21 and p27; and it is found that hypophosphorylation of retinoblastoma protein in Hypoxia is Hif-1 α dependent.

Hypoxia-inducible factor-1alpha is a critical mediator of hypoxia induced apoptosis in cardiac H9c2 and kidney epithelial HK-2 cells

It is demonstrated that HIF-1α is an important component of the apoptotic signaling machinery in the two cell types and upregulation of the pro-apoptotic protein, Bax, was found in H9c2 cells overexpressing full-length pcDNA3-HA-Hif-1 α exposed to hypoxia.

Interaction between PARP-1 and HIF-2α in the hypoxic response

A complex functional interaction between PARP-1 and the HIF system is revealed and it is suggested that parp-1 is involved in the fine tuning of the Hif-mediated hypoxic response in vivo.

Hif-1α Knockdown Reduces Glycolytic Metabolism and Induces Cell Death of Human Synovial Fibroblasts Under Normoxic Conditions

It is demonstrated that SF are highly dependent on glycolytic metabolism and that HIF-1α plays a regulatory role in glycoleysis even under aerobic conditions and that local targeting of Hif-1 α provides a feasible strategy to reduce SF hyperplasia in chronic arthritic diseases.

Hypoxia-directed cancer therapy

Hypoxia-inducible factor 1, a transcriptional activator composed of an O2 - and growth factor-regulated Hif-1α subunit and a constitutively expressed HIF-1β subunit, is a potential anticancer target.



Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha.

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.

Oxygen(es) and the hypoxia-inducible factor-1.

A survey of the bH LH-PAS family as well as of the genes regulated by HIF-1, and a summary of the current knowledge on the oxygen-dependent activation of this fascinating transcription factor are presented.

Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth.

Findings show that HIF-1 activation occurs in hypoxic regions of tumors and demonstrate a major influence on gene expression, tumor angiogenesis, and growth.

Regulation of Proliferation-Survival Decisions during Tumor Cell Hypoxia

To examine mechanisms underlying growth-survival decisions during hypoxia, genetically related transformed and untransformed fibroblast cells in vitro are compared in vitro for proliferation, survival, clonogenicity, cell cycle, and p53 expression.

Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT

A model in which increasing tissue mass during organogenesis leads to the formation of hypoxic/nutrient-deprived cells, the subsequent activation of ARNT, and a concomitant increase in the expression of genes that promote vascularization of the developing yolk sac and solid tissues is proposed.

Dimerization, DNA Binding, and Transactivation Properties of Hypoxia-inducible Factor 1*

Structural features of the HIF-1α subunit that are required for heterodimerization, DNA binding, and transactivation of hypoxia-inducible factor 1 are reported.

Hypoxia induces accumulation of p53 protein, but activation of a G1-phase checkpoint by low-oxygen conditions is independent of p53 status

Hypoxia is an example of a "nongenotoxic" stress which induces p53 activity by a different pathway than DNA-damaging agents, and cells expressing the human papillomavirus E6 gene, which show increased degradation of p53 by ubiquitination and fail to accumulate p53 in response to DNA-damage agents, do increase their p53 levels following heat and hypoxia.

Oxygen sensing and molecular adaptation to hypoxia.

Redox chemistry appears to play a critical role both in the trans-activation of oxygen-responsive genes in unicellular organisms as well as in the activation of HIF-1, which is required for the hypoxic induction of physiologically important genes.

Selection and analysis of a mutant cell line defective in the hypoxia-inducible factor-1 alpha-subunit (HIF-1alpha). Characterization of hif-1alpha-dependent and -independent hypoxia-inducible gene expression.

The utility of mutagenesis and selection of mutant cells in the analysis of mammalian transcriptional responses to hypoxia is shown and the operation of HIF-1alpha-dependent and Hif-1 alpha-independent pathways of hypoxIA-inducible gene expression in Chinese hamster ovary cells is demonstrated.