Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • Allergy (Apr 2019)
    • Biology of familial cancer predisposition syndromes (Feb 2019)
    • Mitochondrial dysfunction in disease (Aug 2018)
    • Lipid mediators of disease (Jul 2018)
    • Cellular senescence in human disease (Apr 2018)
    • View all review series...
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Scientific Show Stoppers
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication
Hypoxia-inducible factors: a central link between inflammation and cancer
Daniel Triner, Yatrik M. Shah
Daniel Triner, Yatrik M. Shah
Published October 3, 2016; First published August 15, 2016
Citation Information: J Clin Invest. 2016;126(10):3689-3698. https://doi.org/10.1172/JCI84430.
View: Text | PDF
Category: Review Series

Hypoxia-inducible factors: a central link between inflammation and cancer

  • Text
  • PDF
Abstract

The tumor immune response is in a dynamic balance between antitumor mechanisms, which serve to decrease cancer growth, and the protumor inflammatory response, which increases immune tolerance, cell survival, and proliferation. Hypoxia and expression of HIF-1α and HIF-2α are characteristic features of all solid tumors. HIF signaling serves as a major adaptive mechanism in tumor growth in a hypoxic microenvironment. HIFs represent a critical signaling node in the switch to protumorigenic inflammatory responses through recruitment of protumor immune cells and altered immune cell effector functions to suppress antitumor immune responses and promote tumor growth through direct growth-promoting cytokine production, angiogenesis, and ROS production. Modulating HIF function will be an important mechanism to dampen the tumor-promoting inflammatory response and inhibit cancer growth.

Authors

Daniel Triner, Yatrik M. Shah

×

Figure 1

Activation of HIFs by hypoxia and inflammation.

Options: View larger image (or click on image) Download as PowerPoint
Activation of HIFs by hypoxia and inflammation.
(A) HIF-α subunits are r...
(A) HIF-α subunits are regulated by posttranslational hydroxylation of two specific proline residues by PHD enzymes in normoxic conditions. This leads to VHL-mediated proteasomal degradation. As O2 concentration drops or mitochondrial ROS production increases HIF-α subunits are stabilized, dimerize with ARNT, and translocate to the nucleus and bind to HRE sequences in target genes. (B) HIFs are activated by inflammation through cytokine-induced Hif2α expression, NF-κB–mediated transcription of Hif1α, NF-κB–dependent ferritin iron sequestration, cytokine-mediated mitochondrial ROS production, and the TCA metabolite succinate.
Follow JCI:
Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts