title: SEPT7 overexpression inhibits glioma cell migration by targeting the actin cytoskeleton pathway.
abstract: Glioma cell metastasis is a serious obstacle for surgical treatment and prognosis, of which locomotion of the cytoskeleton is a key contributor of cancer cell spreading. SEPT7 is documented as a cytoskeletal protein with GTPase activity and involved in glioma progression. However, the underlying mechanism of SEPT7 in glioma invasion remains unresolved. Our study investigated whether SEPT7 influences glioma cell migration involved in cytoskeleton modulation. The SEPT7 expression in various glioma cell lines was markedly decreased compared to in normal human brain cells. It was demonstrated that SEPT7 overexpression significantly inhibits LN18 cell migration and chemotaxis induced by IGF‑1 (P<0.01 and P<0.01). Moreover, MMP‑2 and MMP‑9 were dramatically depressed after SEPT7 upregulation. To understand the mechanisms by which SEPT7 modulates homeostasis of the actin cytoskeleton, the F‑actin/G‑actin ratio and cofilin expression were determined. The data revealed that the F‑actin/G‑actin ratio and cofilin were reduced, and p‑cofilin increased conversely in cells with SEPT7 overexpression, indicating that SEPT7 reduced glioma cell migration by promoting cofilin phosphorylation and depolymerizing actin. Then, to understand the role of cofilin in SEPT7‑mediated actin dynamic equilibrium and cell migration, cofilin siRNA was transfected into cells. Surprisingly, cell migration and actin polymerization which had been improved by SEPT7 siRNA were significantly reversed, and the accompanying cofilin phosphorylation increased, indicating that cofilin phospho‑regulation played an important role in SEPT7‑mediated cytoskeleton locomotion and glioma cell migration. In conclusion, SEPT7 is involved in glioma cell migration with the assistance of cofilin phospho‑mediated cytoskeleton locomotion.
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
authors: Mingshan
authors: M
authors: Hou
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
authors: Xiaobing
authors: X
authors: Liu
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
authors: Jie
authors: J
authors: Cao
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
authors: Bo
authors: B
authors: Chen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D010766:Phosphorylation; D058112:Septins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051339:Actin Depolymerizing Factors; D018797:Cell Cycle Proteins; C113158:SEPTIN7 protein, human; D058112:Septins