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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 / Copyright

    Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2107-2112
    |
    Published online on: June 15, 2017
       https://doi.org/10.3892/mmr.2017.6794
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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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View References

1 

Mizushima N, Levine B, Cuervo AM and Klionsky DJ: Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Levine B and Kroemer G: Autophagy in the pathogenesis of disease. Cell. 132:27–42. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Cao J, Ying M, Xie N, Lin G, Dong R, Zhang J, Yan H, Yang X, He Q and Yang B: The oxidation states of DJ-1 dictate the cell fate in response to oxidative stress triggered by 4-hpr: Autophagy or apoptosis? Antioxid Redox Signal. 21:1443–1459. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Rubinsztein DC: The roles of intracellular protein-degradation pathways in neurodegeneration. Nature. 443:780–786. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Yang Z and Klionsky DJ: Eaten alive: A history of macroautophagy. Nat Cell Biol. 12:814–822. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Mijaljica D, Prescott M and Devenish RJ: Microautophagy in mammalian cells: Revisiting a 40-year-old conundrum. Autophagy. 7:673–682. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Jiang P and Mizushima N: Autophagy and human diseases. Cell Res. 24:69–79. 2014. View Article : Google Scholar : PubMed/NCBI

8 

White E: Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 12:401–410. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Burada F, Nicoli ER, Ciurea ME, Uscatu DC, Ioana M and Gheonea DI: Autophagy in colorectal cancer: An important switch from physiology to pathology. World J Gastrointest Oncol. 7:271–284. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Cecconi F and Jäättelä M: Targeting ions-induced autophagy in cancer. Cancer cell. 26:599–600. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Shintani T and Klionsky DJ: Autophagy in health and disease: A double-edged sword. Science. 306:990–995. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Sena P, Mariani F, Mancini S, Benincasa M, Magnani G, Pedroni M, Palumbo C and Roncucci L: Autophagy is upregulated during colorectal carcinogenesis, and in DNA microsatellite stable carcinomas. Oncol Rep. 34:3222–3230. 2015.PubMed/NCBI

13 

Shelby SJ, Angadi PS, Zheng QD, Yao J, Jia L and Zacks DN: Hypoxia inducible factor 1α contributes to regulation of autophagy in retinal detachment. Exp Eye Res. 137:84–93. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB, Gonzalez FJ and Semenza GL: Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem. 283:10892–10903. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Zhu H, Wang D, Zhang L, Xie X, Wu Y, Liu Y, Shao G and Su Z: Upregulation of autophagy by hypoxia-inducible factor-1α promotes EMT and metastatic ability of CD133+ pancreatic cancer stem-like cells during intermittent hypoxia. Oncol Rep. 32:935–942. 2014.PubMed/NCBI

16 

Wang GL, Jiang BH, Rue EA and Semenza GL: Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA. 92:5510–5514. 1995. View Article : Google Scholar : PubMed/NCBI

17 

Blagosklonny MV: Antiangiogenic therapy and tumor progression. Cancer cell. 5:13–17. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Semenza GL: HIF-1 and mechanisms of hypoxia sensing. Curr Opin Cell Biol. 13:167–171. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Seeber LM, Horrée N, Vooijs MA, Heintz AP, van der Wall E, Verheijen RH and van Diest PJ: The role of hypoxia inducible factor-1alpha in gynecological cancer. Crit Rev Oncol Hematol. 78:173–184. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Tittarelli A, Janji B, van Moer K, Noman MZ and Chouaib S: The selective degradation of synaptic connexin 43 protein by Hypoxia-induced autophagy impairs natural killer cell-mediated tumor cell killing. J Biol Chem. 290:23670–23679. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Jiang H, Martin V, Gomez-Manzano C, Johnson DG, Alonso M, White E, Xu J, McDonnell TJ, Shinojima N and Fueyo J: The RB-E2F1 pathway regulates autophagy. Cancer Res. 70:7882–7893. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Chen T, Xue L, Niu J, Ma L, Li N, Cao X, Li Q, Wang M, Zhao W, Li G, et al: The retinoblastoma protein selectively represses E2F1 targets via a TAAC DNA element during cellular senescence. J Biol Chem. 287:37540–37551. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Polager S and Ginsberg D: E2F-at the crossroads of life and death. Trends Cell Biol. 18:528–535. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD and Levine B: Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 122:927–939. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Luo S and Rubinsztein DC: Apoptosis blocks Beclin 1-dependent autophagosome synthesis: An effect rescued by Bcl-xL. Cell Death Differ. 17:268–277. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Chagin AS: Effectors of mTOR-autophagy pathway: Targeting cancer, affecting the skeleton. Curr Opin Pharmacol. 28:1–7. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Pei Y, Wang P, Liu H, He F and Ming L: FOXQ1 promotes esophageal cancer proliferation and metastasis by negatively modulating CDH1. Biomed Pharmacother. 74:89–94. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Kirschner K, Samarajiwa SA, Cairns JM, Menon S, Pérez-Mancera PA, Tomimatsu K, Bermejo-Rodriguez C, Ito Y, Chandra T, Narita M, et al: Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53. PLoS Genet. 11:e10050532015. View Article : Google Scholar : PubMed/NCBI

29 

Vaupel P: The role of hypoxia-induced factors in tumor progression. Oncologist. 9 Suppl 5:S10–S17. 2004. View Article : Google Scholar

30 

Unruh A, Ressel A, Mohamed HG, Johnson RS, Nadrowitz R, Richter E, Katschinski DM and Wenger RH: The hypoxia-inducible factor-1 alpha is a negative factor for tumor therapy. Oncogene. 22:3213–3220. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Clarke HJ, Chambers JE, Liniker E and Marciniak SJ: Endoplasmic reticulum stress in malignancy. Cancer Cell. 25:563–573. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Zhu Y, Zhao T, Itasaka S, Zeng L, Yeom CJ, Hirota K, Suzuki K, Morinibu A, Shinomiya K, Ou G, et al: Involvement of decreased hypoxia-inducible factor 1 activity and resultant G1-S cell cycle transition in radioresistance of perinecrotic tumor cells. Oncogene. 32:2058–2068. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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