title: SDF-1/CXCR4 Axis Regulates Cell Cycle Progression and Epithelial-Mesenchymal Transition via Up-regulation of Survivin in Glioblastoma.
abstract: Stromal cell-derived factor 1 (SDF-1)/CXCR4 ligand-receptor axis is widely recommended as an attractive target for cancer therapy. Meanwhile, epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. As one of inhibitors of apoptosis proteins, survivin is implicated in the onset and development of cancer. In the present study, we tried to determine the cause-effect associations between SDF-1/CXCR4 axis and survivin expression in glioblastoma U-251 cell line. Survivin activation and inhibition were induced with exogenous SDF-1 and survivin small interfering RNA (survivin siRNA), respectively. Western blot was used to detect relevant proteins in SDF-1/CXCR4 axis. Western blot analysis revealed that survivin expression in U-251 increased in a dose- and time-dependent manner in response to SDF-1 treatment. However, the interference with MEK/ERK and PI3K/AKT pathway prohibited SDF-1-induced survivin up-regulation. Importantly, survivin knockdown abrogated cell cycle progression and the expression of snail and N-cadherin, compared with non-transfectants. In conclusion, the present study shows that SDF-1 up-regulates survivin via MEK/ERK and PI3K/AKT pathway, leading to cell cycle progression and EMT occurrence dependent on survivin. The blockade of survivin will allow for the treatment of glioblastoma.
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, No. 49 Hua Yuan Bei Lu, Beijing, 100191, China. liaoanyan323@126.com.
authors.forename: Anyan
authors.initials: A
authors.lastname: Liao
authors.affiliation: Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, No. 49 Hua Yuan Bei Lu, Beijing, 100191, China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, No. 49 Hua Yuan Bei Lu, Beijing, 100191, China.
authors.forename: Suqing
authors.initials: S
authors.lastname: Tian
authors.affiliation: Shandong University School of Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Li
authors.affiliation: Shandong University School of Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Fuxi
authors.initials: F
authors.lastname: Song
authors.affiliation: Shandong University School of Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, No. 49 Hua Yuan Bei Lu, Beijing, 100191, China.
authors.forename: Jinna
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Haiqin
authors.initials: H
authors.lastname: Yun
authors.affiliation: Department of Pathology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Xiangshan
authors.initials: X
authors.lastname: Yang
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D054377:Chemokine CXCL12 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4 / Q000378:metabolism*; D000077022:Survivin; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation
chemical_list: C107489:BIRC5 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D000077022:Survivin; D051057:Proto-Oncogene Proteins c-akt
keywords: Cell cycle progression; EMT; SDF-1/CXCR4; Survivin