title: CXCL12/CXCR4 Axis Upregulates Twist to Induce EMT in Human Glioblastoma.
abstract: In recent decades, the chemokine receptor CXCR4 and its ligand CXCL12 have been extensively reported to be associated with tumorigenesis. In addition, Twist signaling induces the epithelial-mesenchymal transition (EMT) process in glioblastoma development. In the present study, in vitro assays were used to investigate the role of CXCR4 and Twist in human glioblastoma. We explored the impact of CXCR4 and Twist on human glioblastoma using in vitro protein and gene assays. We found the administration of CXCL12 upregulated the expression of p-ERK, p-AKT, Twist, N-cadherin, and MMP9 in U87 cells, whereas the increase of E-cadherin protein was affected. Subsequently, Twist activity and EMT signaling were directly influenced by PD98059 and LY294002. Most importantly, the genetic silencing of Twist inhibited CXCL12-induced EMT occurrence, including proliferation, migration, and tumor formation of U87 cells. In conclusion, CXCL12/CXCR4 pathway activates ERK and PI3K/AKT signaling to upregulate Twist pathway, leading to the progression of EMT in human glioblastoma. Our study creates a new stage for molecule-targeted therapy of human glioblastoma.
authors.affiliation: Glioma Surgery Division, Neurological Surgery Department, Huashan Hospital, Shanghai Medical College, Fudan University, 12#, Wulumuqi Zhong Road, Shanghai, 200040, China.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Yao
authors.affiliation: School of Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Li
authors.affiliation: School of Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Huishu
authors.initials: H
authors.lastname: Song
authors.affiliation: School of Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Fuxi
authors.initials: F
authors.lastname: Song
authors.affiliation: School of Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Qu
authors.affiliation: School of Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Ma
authors.affiliation: School of Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Shi
authors.affiliation: Glioma Surgery Division, Neurological Surgery Department, Huashan Hospital, Shanghai Medical College, Fudan University, 12#, Wulumuqi Zhong Road, Shanghai, 200040, China. wujssh@126.com.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wu
keywords: CXCR4; EMT; Human glioblastoma; Twist