Role of hypoxia inducible factor 1α as a potential target in cancer therapy
Hypoxia inducible factor (HIF) is a heterodimer transcription factor composed of one of three alpha (α) subunits and a beta (β) subunit. The expression of HIF-α is induced under hypoxic conditions, HIF-1α and HIF-2α are shown to be regulator in transcriptional response to hypoxia, they have similar protein structure (48% amino acid sequence similarity), but different target genes and regulatory mechanism. HIF3α is the newest member of the family and its role is still unclear. HIF-1β is constitutively expressed, which is a partner of aryl hydrocarbon receptor (AhR) it binds to AhR helping its translocation to the nucleus, so it is also referred to as aryl hydrocarbon nuclear translocator (ARNT). HIF-1α is encoded by HIF1A gene, which is located in chromosome 14, that is expressed in most tissues with highest levels in kidneys and heart
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Our cells response to low oxygen tension (hypoxia) by transcriptional induction of a series of genes, this induction is mediated by hypoxia-inducible factors (HIFs), which are family of transcription factors consist of one of three α subunits (HIF-1α, HIF-2α, HIF-3α) and β subunit (HIF-1β). HIF-1α expression is induced by hypoxia, it was found that it is a master regulator of angiogenesis and plays a critical role in glucose metabolic pathways which provide physiologic adaptation and cell survival during hypoxic conditions. Clinical investigations have been shown a correlation between overexpression of HIF-1 and aggressive cancer progression, which may be expected considering the fact that cancer cells are known to be hypoxic. Thus, targeting HIF-1 could represent a novel approach to cancer therapy, as it allows for survival and proliferation of cancerous cells due to its angiogenic and metabolic properties
