Hypoxia-inducible factors as key regulators of tumor inflammation

Authors

  • Soulafa Mamlouk,

    1. Emmy Noether Research Group and Institute of Pathology, University of Technology, Dresden, Germany
    Search for more papers by this author
  • Ben Wielockx

    Corresponding author
    1. Emmy Noether Research Group and Institute of Pathology, University of Technology, Dresden, Germany
    2. DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden, University of Technology, Dresden, Germany
    • Emmy Noether Group Leader (DFG), Inst. of Pathology, University of Technology Dresden, Schubertstrasse 15, D-01307 Dresden, Germany
    Search for more papers by this author
    • Fax: +49-351-4584328


Abstract

Low levels of oxygen or hypoxia is often an obstacle in health, particularly in pathological disorders like cancer. The main family of transcription factors responsible for cell survival and adaptation under strenuous conditions of hypoxia are the “hypoxia-inducible factors” (HIFs). Together with prolyl hydroxylase domain enzymes (PHDs), HIFs regulates tumor angiogenesis, proliferation, invasion, metastasis, in addition to resistance to radiation and chemotherapy. Additionally, the entire HIF transcription cascade is involved in the “seventh” hallmark of cancer; inflammation. Studies have shown that hypoxia can influence tumor associated immune cells toward assisting in tumor proliferation, differentiation, vessel growth, distant metastasis and suppression of the immune response via cytokine expression alterations. These changes are not necessarily analogous to HIF's role in non-cancer immune responses, where hypoxia often encourages a strong inflammatory response.

Ancillary