Detail for HIF-1α


Full Name

Hypoxia-inducible factor 1-α

Uniprot ID

Gene Name

HIF1A

NCBI ID

Related Disease

  • Prostate Cancer [ref.1, 2]
  • Multiple Myeloma [ref.3]
  • Breast cancer [ref.4,7]
  • Glioblastoma [ref.5]
  • Colorectal cancer [ref.6]

Therapy Method

Function

Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcription coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.

Reference

  • [1] Hypoxia induced aggressiveness of prostate cancer cells is linked with deregulated expression of VEGF, IL-6 and miRNAs that are attenuated by CDF.
    Bao, B., et al. (2012). PLoS One 7(8): e43726.. [ 22952749 ]
  • [2] Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment.
    Bao, B., et al. (2012). PLoS One 7(12): e50165.. [ 23272057 ]
  • [3] Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1.Hawley, T. S., et al. (2013). Am J Hematol 88(4): 265-272.
    23475625. [ 23475625 ]
  • [4] Hypoxia-inducible factors: coupling glucose metabolism and redox regulation with induction of the breast cancer stem cell phenotype.
    EMBO J.2017 Feb 1;36(3):252-259. [ 28007895 ]
  • [5] Targeting Hypoxia-Inducible Factor 1α in a New Orthotopic Model of Glioblastoma Recapitulating the Hypoxic Tumor Microenvironment.
    J Neuropathol Exp Neurol.2015 Jul;74(7):710-22. [ 26083570 ]
  • [6] Hypoxic tumor microenvironment activates GLI2 via HIF-1α and TGF-β2 to promote chemoresistance in colorectal cancer.
    Proc Natl Acad Sci U S A.2018 Jun 26;115(26):E5990-E5999. [ 29891662 ]
  • [7] ITGA6 is directly regulated by hypoxia-inducible factors and enriches for cancer stem cell activity and invasion in metastatic breast cancer models.
    Mol Cancer.2016 Mar 22;15:26. [ 27001172 ]
  • [8] HIF expression and the role of hypoxic microenvironments within primary tumours as protective sites driving cancer stem cell renewal and metastatic progression.
    Carcinogenesis.2013 Aug;34(8):1699-707. [ 23740838 ]

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