Figure 2.

Hypoxia regulates tumour progression via various mechanisms, including HIF independent (blue arrow) and HIF-dependent manner (black arrow). Intratumoural hypoxia causes overexpression of HIF-1α and HIF-2α, leading to transactivation of multiple target genes outlined above. These regulate the cellular response to CSCs maintenance, EMT induction, angiogenesis, metabolic reprogramming, and immunosuppression. Tumour progression is also influenced by numerous HIF-independent factors including miRNA expression and cytokine release, activating various pro-tumour signalling pathways. Abbreviations: IL-6, interleukin 6; SV, supervillain; PIP2, phosphatidylinositol (4,5) biphosphate; RORA, RAR-related orphan receptor; MDSCs, myeloid-derived suppressor cells; TAMs, tumour-associated macrophages; Treg, regulatory T cells; CTLs, cytotoxic T lymphocytes.