title: Nuclear Protein C23 on the Cell Surface Plays an Important Role in Activation of CXCR4 Signaling in Glioblastoma.
abstract: The chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 (SDF-1) plays an important role in tumor progression and are associated with angiogenesis. Meanwhile, the implications of C23 in multiple signaling pathways have been also investigated. However, the effects of C23 on CXCR4 pathway in glioblastoma are not fully characterized. In the present study, C23 and CXCR4 of U87 cell line were inhibited by anti-C23 and anti-CXCR4 antibodies, respectively; and then C23 and CXCR4 siRNAs were used to knock down endogenous C23 and CXCR4, respectively. In addition, MTT assay was also introduced. Our data showed that either anti-C23 or anti-CXCR4 antibodies efficaciously repressed the phosphorylation levels of ERK (p < 0.000) and AKT (p < 0.000) compared with SDF-1 alone and control. As expected, either C23 or CXCR4 siRNAs indeed resulted in C23 and CXCR4 knockdown and further suppressed the expression of p-ERK and p-AKT. Most importantly, immunoprecipitation revealed C23 interacted with CXCR4 once U87 was exposed to SDF-1 treatment. In addition, MTT assay identified that C23 or CXCR4 siRNAs could obviously decreased cell proliferation capacity (p = 0.002). In conclusion, our results suggest that C23 plays a crucial role in activation of SDF-1-induced ERK and PI3K/AKT pathways via interacting with CXCR4. Furthermore, C23 could be recommended as an important element in glioblastoma development and a new target for glioblastoma treatment.
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
authors.forename: Congxin
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.|Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Shunzeng
authors.initials: S
authors.lastname: Lv
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Shi
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Paediatrics, Xiaolan People's Hospital Affiliated to Southern Medical University, Zhongshan, Guangdong, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Huishu
authors.initials: H
authors.lastname: Song
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Ma
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
authors.forename: Renzhi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China. mwbpumch@163.com.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001932:Brain Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D000097796:Nucleolin
chemical_list: D000906:Antibodies; D054377:Chemokine CXCL12; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D000097796:Nucleolin; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; C494918:AKT1 protein, human
keywords: C23; CXCR4 signaling; ERK; Glioblastoma; PI3K/AKT