Open Access

Hypoxia inducible factor-1α regulates autophagy via the p27-E2F1 signaling pathway

  • Authors:
    • Pan Wang
    • Meijing Long
    • Shijie Zhang
    • Zhenyun Cheng
    • Xin Zhao
    • Fucheng He
    • Hongchun Liu
    • Liang Ming
  • View Affiliations

  • Published online on: June 15, 2017     https://doi.org/10.3892/mmr.2017.6794
  • Pages: 2107-2112
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Autophagy is a highly conserved process by which the cell contents are delivered to lysosomes for degradation, or are used to provide macromolecules for energy generation under conditions of nutritional starvation. It has previously been demonstrated that cancer cells in hypoxic regions, with an oxygen concentration below the normal physiological level, express hypoxia inducible factor (HIF)‑1α, in order to adapt and survive. HIF‑1α is important in the regulation of oxygen homeostasis and the transcription of hundreds of genes in response to conditions of hypoxia, hence maintaining energy and redox homeostasis. To determine if HIF‑1α modulates autophagy and the underlying molecular mechanisms regulating this process, the human esophageal cancer EC109 and IMR90 human diploid fibroblast cell lines were exposed to normoxic or hypoxic conditions and the expression levels of various proteins subsequently examined. Small interfering RNA was used to silence p27, in order to investigate its role in the process of HIF‑1α regulated autophagy. Hypoxia induced autophagy in IMR90 cells and it was revealed that immature IMR90 cells demonstrated an increased rate of autophagy compared with mature cells. HIF‑1α promoted EC109 cell autophagy via positively modulating p27, whereas silencing of p27 abolished the autophagy induced by hypoxia. The present study identified the primary components of the p27‑E2F1 signaling pathway by which HIF‑1α regulates autophagy. A previously unidentified mechanism is here presented, via which cancer cells may generate energy, or obtain macromolecules for survival.
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August-2017
Volume 16 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wang P, Long M, Zhang S, Cheng Z, Zhao X, He F, Liu H and Ming L: Hypoxia inducible factor-1α regulates autophagy via the p27-E2F1 signaling pathway. Mol Med Rep 16: 2107-2112, 2017
APA
Wang, P., Long, M., Zhang, S., Cheng, Z., Zhao, X., He, F. ... Ming, L. (2017). Hypoxia inducible factor-1α regulates autophagy via the p27-E2F1 signaling pathway. Molecular Medicine Reports, 16, 2107-2112. https://doi.org/10.3892/mmr.2017.6794
MLA
Wang, P., Long, M., Zhang, S., Cheng, Z., Zhao, X., He, F., Liu, H., Ming, L."Hypoxia inducible factor-1α regulates autophagy via the p27-E2F1 signaling pathway". Molecular Medicine Reports 16.2 (2017): 2107-2112.
Chicago
Wang, P., Long, M., Zhang, S., Cheng, Z., Zhao, X., He, F., Liu, H., Ming, L."Hypoxia inducible factor-1α regulates autophagy via the p27-E2F1 signaling pathway". Molecular Medicine Reports 16, no. 2 (2017): 2107-2112. https://doi.org/10.3892/mmr.2017.6794