White Paper: The Cellular Response to Hypoxia in Cancer

This white paper provides an overview of hypoxia in cancer. The key role of HIF transcription factors as master regulators of hypoxia adaptations in cancer and recent findings on the differential responses elicited by acute vs chronic hypoxia are highlighted.

Learn about the crucial role of hypoxia in cancer

• Key domains in HIF proteins
• Regulation of HIF proteins in normoxia
• HIF target genes
• Cellular adaptations promoting tumorigenesis

Abstract

Tissue hypoxia exerts significant influence on molecular programs, cellular properties and in tumors often leads to aggressive phenotypes. HIF-1α and HIF-2α belong to the family of hypoxia inducible transcription factors and mediate cellular reprograming under low oxygen conditions. HIFs are stabilized under hypoxia and regulate the expression of genes involved in key cellular adaptations including angiogenesis, metabolic switch and stemness. A standing question in the cancer research field is how variability in the duration of hypoxia affects cellular adaptations and tumorigenesis. Acute and chronic hypoxia co-exist in tumors and differentially shape the phenotype of cancer cells. Differential responses to acute vs chronic hypoxia are partly underscored by differences in the recruitment of HIF-1α vs HIF-2α. Here, we provide an overview of key cellular adaptations triggered by hypoxia and emphasize recent findings highlighting the role of hypoxia-duration in shaping cancer cell phenotypes.