title: Mitochondrial dynamics regulates hypoxia-induced migration and antineoplastic activity of cisplatin in breast cancer cells.
abstract: Mitochondria are high dynamic organelles with frequent fission and fusion. Here, we found hypoxia stimulated Drp1 expression, mitochondrial fission and migration in metastatic MDA-MB‑231 cells, but not in non-metastatic MCF-7 cells. Inhibition of Drp1-dependent mitochondrial fission by Mdivi-1 or silencing Drp1 attenuated hypoxia-induced mitochondrial fission and migration in MDA-MB‑231 cells. On the other hand, cisplatin induced significant apoptosis and mitochondrial fission in MDA-MB‑231 cells, but not in MCF-7 cells. Mdivi-1 and silencing Drp1 also efficiently prevented cisplatin-induced MMP decrease, ROS production and apoptosis in MDA-MB‑231 cells. Our data suggest that Drp1-dependent mitochondrial fission not only regulates hypoxia-induced migration of breast cancer cells, but also facilitates its sensitivity to chemotherapeutic agents. Thus, targeting Drp1-dependent mitochondrial dynamics may provide a novel strategy to suppress breast cancer metastasis and improve the chemotherapeutic effect in the future.
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, P.R. China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Han
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, P.R. China.
authors.forename: Zhang-Jian
authors.initials: ZJ
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, P.R. China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jiang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, P.R. China.
authors.forename: Yong-Fang
authors.initials: YF
authors.lastname: Wei
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, P.R. China.
authors.forename: Ming-Fang
authors.initials: MF
authors.lastname: Liao
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, P.R. China.
authors.forename: Yisong
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, P.R. China.
authors.forename: Jian-Bin
authors.initials: JB
authors.lastname: Wang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, P.R. China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Xin
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, P.R. China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Wan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D034281:Dynamins; D005260:Female; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006801:Humans; D061986:MCF-7 Cells; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D063154:Mitochondrial Dynamics / Q000187:drug effects* / Q000235:genetics; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052999:Quinazolinones / Q000008:administration & dosage
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D052999:Quinazolinones; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins; D002945:Cisplatin