Defining the Role of Hypoxia-Inducible Factor 1 in Cancer Biology and Therapeutics

By G. Semenza. Oncogene, 2009

1,739 citations recorded by the source corpus.

Adaptation of cancer cells to their microenvironment is an important driving force in the clonal selection that leads to invasive and metastatic disease. O2 concentrations are markedly reduced in many human cancers compared with normal tissue, and a major mechanism mediating adaptive responses to reduced O2 availability (hypoxia) is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). This review summarizes the current state of knowledge regarding the molecular mechanisms by which HIF-1 contributes to cancer progression, focusing on (1) clinical data associating increased HIF-1 levels with patient mortality; (2) preclinical data linking HIF-1 activity with tumor growth; (3) molecular data linking specific HIF-1 target gene products to critical aspects of cancer biology and (4) pharmacological data showing anticancer effects of HIF-1 inhibitors in mouse models of human cancer.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/cec2d5e98a70df34ed1e0b844b842fab8daf853c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

Thyroid hormone regulation of metabolism. (2014, background): “tion to hypoxia in tumor cells that results in expression of glycolytic enzymes and glucose transporters (222).”
The oncometabolite 2‐hydroxyglutarate inhibits histone lysine demethylases (2011, background): “HIF target genes encode proteins that enable tumour growth, including vascular endothelial growth factor (Semenza, 2010).”
Hallmarks of cancer: the next generation. (2011, positive): “…can be further accentuated under the hypoxic conditions that operate within many tumors: the hypoxia response system acts pleio-tropically to upregulate glucose transporters and multiple enzymes of the glycolytic pathway (Semenza, 2010a; Jones and Thompson, 2009; DeBerardinis et al., 2008).”
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. (2013, neutral): “Increased HIF-1 α levels are also associated with increased risk of mortality in many human cancers, including those of the bladder, brain, breast, colon, esophagus, head/neck/oropharynx, liver, lung, pancreas, skin, stomach, and uterus, as well as in acute lymphocytic and myeloid leukemias (15).”
Pyruvate Kinase M2 is a PHD3-stimulated Coactivator for Hypoxia-Inducible Factor 1 (2011, positive): “PHD3 knockdown reduces glucose uptake and lactate production and increases O2 consumption in VHL null renal cancer cells.”
Hypoxic Tumor-Derived Exosomal miR-301a Mediates M2 Macrophage Polarization via PTEN/PI3Kγ to Promote Pancreatic Cancer Metastasis. (2018, background): “The major mechanism mediating cellular responses to hypoxia is stabilization and activation of hypoxia-inducible factors (HIF), especially HIF1a and HIF2a, which activate a set of genes that facilitate tumor growth, angiogenesis, and metastasis (9, 10).”
Role of hypoxia in cancer therapy by regulating the tumor microenvironment (2019, background): “Under hypoxic conditions, the inhibitory hydroxylation of HIF-α is reduced, leading to the stability and translocation of HIF-α to the nucleus, where it heterodimerizes with HIF-β [21].”
ISMARA: automated modeling of genomic signals as a democracy of regulatory motifs (2014, background): “Many of the TFs that ISMARA identifies as disregulated in cancer are well-known in cancer biology, including HIF1A[40] (Suppl.”
Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy (2012, background): “An extensive body of experimental and clinical data has validated HIFs as targets for cancer therapy: first, in addition to intratumoral hypoxia, loss-of-function for tumor suppressor genes (most notably, VHL) and gain-of-function for oncogenes and viral transforming genes increase HIF activity (Fig”
Prostate Cancer (2018, background): “The MRI-targeted biopsy was responsible for reclassification in 20% of patients [27].”