Hypoxia-inducible factors (HIFs) are oxygen-sensitive transcription factors that allow adaptation to hypoxic environments. HIFs function in the cellular response to stress: metabolic, hypoxic, or inflammatory. Metabolic changes occur during tumorigenesis that are, in part, under hypoxia and HIF regulation. Additionally, inflammatory signaling and infiltration secondary to hypoxia are clear drivers of tumor progression. HIF-1α and HIF-2α have opposing and occasionally overlapping roles in both tumor cells and inflammatory cells within the tumor microenvironment and crosstalk between these populations has clear effects on tumor metabolism, inflammation, and progression. It is becoming increasingly apparent that HIFs are one common link between hypoxia, chronic inflammation, metabolic adaptation, and tumor progression through its function in macrophages during cancer development.
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