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Review
. 2020 Jun 24:20:273.
doi: 10.1186/s12935-020-01370-0. eCollection 2020.

Implications of HIF-1α in the tumorigenesis and progression of pancreatic cancer

Xiao Jin  1 , Lu Dai  1 , Yilan Ma  1 , Jiayan Wang  1 , Zheng Liu  1
Affiliations
Review

Implications of HIF-1α in the tumorigenesis and progression of pancreatic cancer

Xiao Jin et al. Cancer Cell Int. .

Abstract

Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide and is characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1 alpha (HIF-1α) is a major regulator of cellular response to changes in oxygen concentration, supporting the adaptation of tumor cells to hypoxia in an oxygen-deficient tumor microenvironment. Numerous studies revealed the central role of HIF-1α in the carcinogenesis and progression of pancreatic cancer. This article reviewed the molecular mechanisms of how HIF-1α regulated tumorigenesis and progression of pancreatic cancer and suggested that targeting HIF-1α and its signaling pathways could be promising therapeutics for pancreatic cancer.

Keywords: HIF-1α; Hypoxia; Pancreatic cancer; Progression; Review; Tumorigenesis.

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Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
HRE core sequence
Fig. 2
Fig. 2
HIF-1α degradation and activation. ↑, promote. Under normoxia, HIF-1α is hydroxylated by prolyl hydroxylases and binds to VHL which recruits E3-ubiquitin ligase to interact with HIF-1α, resulting in degradation of HIF-1α in a ubiquitin–proteasome way. Besides, the existence of ROS in normoxia inhibits the acetylation of HIF-1α via blocking the activation of PHDs, protecting HIF-1α from degradation. In hypoxia, oxygen deficiency inhibits hydroxylation of HIF-1α, HIF-1α forms heterodimers with HIF-1β with help of CBP/p300 and transfers to the nucleus to bind to its target genes
Fig. 3
Fig. 3
Signaling pathways induced by HIF-1α in pancreatic cancer tumorigenesis and progression. ↑, promote; Τ, inhibit; ׀, recruit
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