title: TPX2 promotes glioma cell proliferation and invasion via activation of the AKT signaling pathway.
abstract: Glioblastoma multiforme (GBM) is the most common and most malignant type of primary adult brain cancer. The most common phenotype associated with GBM is cellular invasion; however, the molecular mechanisms governing this process are poorly understood. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a nuclear protein with roles in cellular proliferation and mitotic spindle assembly. TPX2 is overexpressed in various malignancies, including human malignant astrocytoma. Despite this finding, the exact role of TPX2 in human glioma is not well defined. The present study reports the elevated expression of TPX2 in a number of glioma cell lines. TPX2 overexpression promoted cellular proliferation, decreased the percentage of cells in G0/G1 phase, and increased invasion of both U251 and U87 cells. Overexpression of TPX2 also significantly enhanced the phosphorylation of AKT, decreased the expression of p21, and increased the expression of cyclin D1 and matrix metallopeptidase (MMP)-9. In both U251 and U87 cells, knockdown of TPX2 resulted in phenotypes that are in direct contrast to those observed following TPX2 overexpression. Specifically, TPX2 knockdown inhibited cell proliferation, increased the percentage of cells in G0/G1 phase, inhibited invasion, decreased AKT phosphorylation, decreased the expression of MMP-9 and cyclin D1, and increased p21 expression. The AKT inhibitor IV in large part phenocopied the effect of TPX2 knockdown. The present data suggest that TPX2 promotes glioma cell proliferation and invasion via AKT signaling.
authors.affiliation: Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, Fuzhou, Fujian 350025, P.R. China; Department of Neurosurgery, Taizhou People's Hospital Affiliated to Medical College of Nantong University, Taizhou, Jiangsu 225300, P.R. China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Gu
authors.affiliation: Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, Fuzhou, Fujian 350025, P.R. China.
authors.forename: Jian-He
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, Fuzhou, Fujian 350025, P.R. China.
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, Fuzhou, Fujian 350025, P.R. China.
authors.forename: Shou-Sen
authors.initials: SS
authors.lastname: Wang
keywords: AKT; TPX2; glioma; invasion; proliferation