Upregulation of autophagy by hypoxia-inducible factor-1α promotes EMT and metastatic ability of CD133+ pancreatic cancer stem-like cells during intermittent hypoxia

  • Authors:
    • Haitao Zhu
    • Dongqing  Wang
    • Lirong  Zhang
    • Xiaodong  Xie
    • Yingying  Wu
    • Yanfang  Liu
    • Genbao  Shao
    • Zhaoliang  Su
  • View Affiliations

  • Published online on: July 2, 2014     https://doi.org/10.3892/or.2014.3298
  • Pages: 935-942
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Abstract

Epithelial-to-mesenchymal transition (EMT) facilitates the escape of pancreatic cancer cells from the primary tumor site, which is a key early event in metastasis. In the present study, we examined if intermittent hypoxia facilitates the invasiveness of human pancreatic cancer cell lines (Panc-1 and BxPC-3) by Transwell assay. We used western blotting and flow cytometry analysis to quantify stem-like cells in the migratory cells during intermittent hypoxia in the human pancreatic cancer cells. Under normoxia or intermittent hypoxia, the expression of autophagy-related proteins (LC3-II and Beclin), hypoxia-inducible factor-1α (HIF-1α) and EMT-related markers (E-cadherin, Vimentin and N-cadherin) was examined by western blotting. siRNA and the autophagic inhibitor were used to access the role of HIF-1α and autophagy in promoting metastasis and EMT. Under intermittent hypoxia, pancreatic cancer cells demonstrated enhanced invasive ability and enriched stem-like cells. The migratory cells displayed stem-like cell characteristics and elevated the expression of LC3-II and Beclin-1, HIF-1α, E-cadherin, Vimentin and N-cadherin under intermittent hypoxia conditions. Moreover, enhanced autophagy was induced by the elevated level of HIF-1α. The metastatic ability and EMT of pancreatic cancer stem cells was associated with HIF-1α and autophagy. This novel finding may indicate the specific role of HIF-1α and autophagy in promoting the metastatic ability of pancreatic cancer stem cells. Additionally, it emphasizes the importance of developing therapeutic strategies targeting cancer stem cells and autophagy to reduce metastasis.
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September-2014
Volume 32 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
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
APA
Zhu, H., Wang, D., Zhang, L., Xie, X., Wu, Y., Liu, Y. ... Su, Z. (2014). Upregulation of autophagy by hypoxia-inducible factor-1α promotes EMT and metastatic ability of CD133+ pancreatic cancer stem-like cells during intermittent hypoxia. Oncology Reports, 32, 935-942. https://doi.org/10.3892/or.2014.3298
MLA
Zhu, H., Wang, D., Zhang, L., Xie, X., Wu, Y., Liu, Y., Shao, G., 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". Oncology Reports 32.3 (2014): 935-942.
Chicago
Zhu, H., Wang, D., Zhang, L., Xie, X., Wu, Y., Liu, Y., Shao, G., 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". Oncology Reports 32, no. 3 (2014): 935-942. https://doi.org/10.3892/or.2014.3298