title: CXCL12-induced upregulation of FOXM1 expression promotes human glioblastoma cell invasion.
abstract: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor; it is highly aggressive and is associated with a poor prognosis. Binding of the chemokine CXCL12 to its receptors (CXCR4 and CXCR7) contributes to the activation of many downstream signaling pathways and promotes the invasion of various malignant tumor cells, including GBM cells. FOXM1, a transcription factor involved in cell cycle regulation, is overexpressed in GBM and is involved in GBM progression. However, the molecular mechanisms by which CXCL12 promotes the invasion of human GBM cells remain unclear. In this study, we demonstrate that CXCL12 increases the production of FOXM1 by binding to CXCR4 in GBM cell lines. Furthermore, pretreatment with an inhibitor of the PI3K/AKT pathway abrogated the CXCL12-induced expression of FOXM1. In addition, there was a positive correlation between CXCL12/CXCR4 expression and FOXM1 expression in human malignant glioma tissues. Finally, a functional assay revealed that CXCL12 does not stimulate GBM cell invasion when FOXM1 expression is silenced using a small interfering RNA (siRNA). Collectively, these findings suggest that CXCL12 promotes GBM cell invasion in part by increasing the expression of FOXM1, which is mediated in part by a PI3K/AKT-dependent mechanism in vitro.
authors.affiliation: Department of Neurosurgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Shengwen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Shanyi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Junliang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Xinke
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Yinlun
authors.initials: Y
authors.lastname: Weng
authors.affiliation: Department of Neurosurgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Meiguang
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Leping
authors.initials: L
authors.lastname: Ouyang
authors.affiliation: Department of Neurosurgery, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China. Electronic address: fangchengli001@163.com.
authors.forename: Fangcheng
authors.initials: F
authors.lastname: Li
mesh_terms: D001254:Astrocytoma / Q000473:pathology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation
chemical_list: D054377:Chemokine CXCL12; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: CXCL12; Chemokine; FOXM1; Glioblastoma; Invasion