title: Involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251 cells.
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.
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Wan
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Zhang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Zhang-Jian
authors.initials: ZJ
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang, Jiangxi, P.R. China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jiang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Yong-Fang
authors.initials: YF
authors.lastname: Wei
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Qi-Nan
authors.initials: QN
authors.lastname: Lai
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Jian-Bin
authors.initials: JB
authors.lastname: Wang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Xin
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Han
mesh_terms: D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D034281:Dynamins; D004448:Echinomycin / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D052999:Quinazolinones / Q000494:pharmacology
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D052999:Quinazolinones; D004448:Echinomycin; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins