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Int J Cancer. 2016 Mar 1;138(5):1058-66. doi: 10.1002/ijc.29519. Epub 2015 Apr 7.

HIF-1 at the crossroads of hypoxia, inflammation, and cancer.

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Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD.


The complex cross-talk of intricate intercellular signaling networks between the tumor and stromal cells promotes cancer progression. Hypoxia is one of the most common conditions encountered within the tumor microenvironment that drives tumorigenesis. Most responses to hypoxia are elicited by a family of transcription factors called hypoxia-inducible factors (HIFs), which induce expression of a diverse set of genes that assist cells to adapt to hypoxic environments. Among the three HIF protein family members, the role of HIF-1 is well established in cancer progression. HIF-1 functions as a signaling hub to coordinate the activities of many transcription factors and signaling molecules that impact tumorigenesis. This mini review discusses the complex role of HIF-1 and its context-dependent partners under various cancer-promoting events including inflammation and generation of cancer stem cells, which are implicated in tumor metastasis and relapse. In addition, the review highlights the importance of therapeutic targeting of HIF-1 for cancer prevention.


HIF-1; cancer stem cells; drug resistance; hypoxia; inflammation; microenvironment

[Available on 2017-03-01]
[Indexed for MEDLINE]
Free PMC Article

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