Approximately 1.0-1.5% of the genome is transcriptionally regulated by
hypoxia, and
hypoxia-inducible factor (HIF)-1α is the
transcription factor modulating many of these genes.
Cancer cells are able to survive hypoxic environments and
hypoxia itself can activate adaptive cellular responses that contribute to
tumor progression. Many HIF-1α-mediated
biological effects are beneficial for
tumor progression, including metabolic shift toward glycolysis, inhibition of
fatty acid β-oxidation, production of cellular
reactive oxygen species and altering expression of tumor suppressor genes. HIF-1 promotes selective mitochondrial autophagy, resistance to T cell mediated lysis of
cancer cells, induction of pluripotent cancer stem cells, epithelial-mesenchymal and epithelial-mesenchymal-endothelial transitions beneficial for
tumor growth and progression, loss of
E-cadherin. HIF-1 also induces production of signal molecules and
cytokines by
carcinoma-associated fibroblasts and upregulation of certain
microRNAs important for
cancer progression. This minireview focuses on the HIF-1 promoting role in
tumor initiation and progression and HIF-1 targeting. HIF-1 pathway downregulation seems to be promising in future
cancer treatment.