title: Superoxide plays critical roles in electrotaxis of fibrosarcoma cells via activation of ERK and reorganization of the cytoskeleton.
abstract: Direct-current electrical field (DCEF) induces directional migration in many cell types by activating intracellular signaling pathways. However, the mechanisms coupling the extracellular electric stimulation to the intracellular signals remain largely unknown. In this study, we show that DCEF directs migration of HT-1080 fibrosarcoma cells to the cathode, stimulates generation of hydrogen peroxide and superoxide through the activation of NADPH oxidase, induces anode-facing cytoskeleton polarization, and activates ERK signaling. Subsequent studies demonstrate that the electrotaxis of HT-1080 fibrosarcoma cells is abolished by NADPH oxidase inhibitor and overexpression of manganese superoxide dismutase (MnSOD), an enzyme that hydrolyzes superoxide. In contrast, overexpression of catalases, which hydrolyze hydrogen peroxide, does not affect electrotaxis. MnSOD overexpression also eliminates cytoskeleton polarization as well as the activation of AKT, ERKs, and p38. In contrast, under catalase overexpression, the cytoskeleton still polarizes and p38 activation is affected. Finally, we show that inhibition of ERK activation also abolishes DCEF-induced directional migration and cytoskeleton polarization. Collectively, our results indicate that superoxide plays critical roles in DCEF-induced directional migration of fibrosarcoma cells, possibly by regulating the activation of ERKs. This study provides novel insights into the current understanding of DCEF-mediated cancer cell directional migration and metastasis.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Chuanshu
authors.initials: C
authors.lastname: Huang
authors.forename: Jiangkai
authors.initials: J
authors.lastname: Lin
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005354:Fibrosarcoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
chemical_list: D013481:Superoxides; D013482:Superoxide Dismutase; D048049:Extracellular Signal-Regulated MAP Kinases