Involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251 cells

  • Authors:
    • Yu-Ying Wan
    • Jian-Feng Zhang
    • Zhang-Jian  Yang
    • Li-Ping  Jiang
    • Yong‑Fang  Wei
    • Qi-Nan  Lai
    • Jian-Bin  Wang
    • Hong-Bo Xin
    • Xiao-Jian Han
  • View Affiliations

  • Published online on: June 5, 2014     https://doi.org/10.3892/or.2014.3235
  • Pages: 619-626
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Abstract

Glioblastoma is one of the most aggressive brain tumors with high morbidity and mortality. Hypoxia is often the common characteristic of tumor microenvironment, and hypoxia-inducible factor-1α (HIF-1α) is an essential factor regulating the migratory activity of cancer cells including glioblastoma. Recently, mitochondrial dynamics was found to be involved in the aggression of cancer cells. However, whether dynamin-related protein 1 (Drp1) contributes to the migration of human glioblastoma cells under hypoxia remains unknown. In the present study, hypoxia was found to upregulate the transcription and expression of Drp1, and stimulated mitochondrial fission in glioblastoma U251 cells. Inhibition of HIF-1α with echinomycin blocked hypoxia‑induced expression of Drp1. Notably, Drp1 inhibitor Mdivi-1 efficiently attenuated hypoxia-induced mitochondrial fission and migration of U251 cells. In addition, three U251 stable cell lines expressing GFP, GFP-Drp1 and dominant negative GFP-Drp1‑K38A were established to examine the direct role of Drp1 in hypoxia-induced migration. MTT assay showed that there was no significant difference in proliferation of three cell lines. Compared with the GFP cell line, exogenously expressed GFP-Drp1-K38A inhibited hypoxia-induced migration of U251 cells, while stable expression of GFP-Drp1 enhanced the migration of U251 cells under hypoxia. Therefore, this study indicates the involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251 cells, and suggests Drp1 to be a potential therapeutic target to suppress the aggression of glioblastoma in the future.
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August-2014
Volume 32 Issue 2

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

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Spandidos Publications style
Wan Y, Zhang J, Yang Z, Jiang L, Wei YF, Lai Q, Wang J, Xin H and Han X: Involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251 cells. Oncol Rep 32: 619-626, 2014
APA
Wan, Y., Zhang, J., Yang, Z., Jiang, L., Wei, Y., Lai, Q. ... Han, X. (2014). Involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251 cells. Oncology Reports, 32, 619-626. https://doi.org/10.3892/or.2014.3235
MLA
Wan, Y., Zhang, J., Yang, Z., Jiang, L., Wei, Y., Lai, Q., Wang, J., Xin, H., Han, X."Involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251 cells". Oncology Reports 32.2 (2014): 619-626.
Chicago
Wan, Y., Zhang, J., Yang, Z., Jiang, L., Wei, Y., Lai, Q., Wang, J., Xin, H., Han, X."Involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251 cells". Oncology Reports 32, no. 2 (2014): 619-626. https://doi.org/10.3892/or.2014.3235