Abstract
Hypoxia-inducible factors (HIFs) are transcription factors that activate the transcription of genes necessary to circumvent to hypoxic (low oxygen level) environments. In carcinogenesis, HIFs play a critical role. Indeed, HIF-1α has been validated as a promising target for novel cancer therapeutics, even as clinical investigations have linked increased levels of HIF-1α with aggressive cancer progression as well as poor patient prognosis. More so, inhibiting HIF-1 activity restricted cancer progression. Therefore, HIF-1 is a viable target for cancer therapy. This may be expected considering the fact that cancer cells are known to be hypoxic. In order to survive the hypoxic microenvironment, cancer cells activate several biochemical pathways via the HIF-1α. Additionally, cellular and molecular insights have proved prospects of the HIF-1α pathway for the development of novel anticancer treatment strategies. The biochemical importance of hypoxia-inducible factors (HIFs) cannot be overemphasized as carcinogenesis, cancer progression, and HIFs are intricately linked. Therefore, this review highlights the significance of these linkages and also the prospects of HIFs as an alternative source of cancer therapies.
Highlights
The function and survival of living organisms are dependent on the adequate supply of oxygen available to the cells
Decreased activities of prolyl hydroxylases (PHDs) and factor inhibiting HIF (FIH) stabilize Hypoxia-inducible factors (HIFs)-α during hypoxia, leading to its translocation to the nucleus, where it subsequently binds with HIF-β to form a complex
Deprivation of oxygen leads to the inhibition of or decreased electron transport chain processes, reducing the mitochondrial membrane potential [55]. This results in the activation of survival/growth factors which are expressed by HIF-regulated genes such as insulin-like growth factor-2 (IGF2), erythropoietin (EPO), vascular endothelial growth factor (VEGF), Endothelin 1 (EDN1), transforming growth factor-α (TGFA), and adrenomedullin [1]
Summary
The function and survival of living organisms are dependent on the adequate supply of oxygen available to the cells. Animals catabolize the sugar from plant using glycolysis, citric acids, and oxidative phosphorylation in an aerobic state During these processes, oxygen is used as an electron acceptor. The consequences of deregulation of hypoxia in cells include breakage of DNA strand, oxidative DNA damage, and gene aberration which hinder cell growth and eventual cellular death. It affects the development of diseases such as chronic lung disease, cancer, diabetes, ischemic heart diseases, stroke, and advanced atherosclerosis [4]. Hypoxia signaling adaptation in a cell is facilitated by the transcriptional regulation family called hypoxia-inducible factor (HIF). The current review is aimed at discussing the prospects of hypoxia-inducible factors as alternative treatment strategy for cancer
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