title: Nucleolin promotes TGF-β signaling initiation via TGF-β receptor I in glioblastoma.
abstract: The transforming growth factor β (TGF-β) pathway plays a key role in oncogenesis of advanced cancers, involving the non-Smad and Smad pathways. Meanwhile, nucleolin on the cell surface has been also reported to affect activation of signaling pathways. However, the effect of cell surface nucleolin on TGF-β pathway in glioblastoma is not still understood. Here, using antibodies of nucleolin and TGF-β receptor I (TβR-I), we observed blocking of either nucleolin or TβR-I inhibited the phosphorylation of CrkL, Erk1/2, and Smad2. Using nucleolin siRNA, nucleolin knockdown was also identified to suppress the expression of p-CrkL, p-Erk1/2, and p-Smad2. Furthermore, immunoprecipitation revealed the interaction between cell surface nucleolin and TβR-I on the U87 cell membrane. In addition, U87 cell wound-healing, soft-agar and MTT assay also showed si-nucleolin could obviously impair wound closure (p < 0.001), colony formation (p < 0.001) and cell growth (p < 0.001). In conclusion, nucleolin promotes and regulates the TGF-β pathway by interacting with TβR-I and is required for initiation and activation of TGF-β signaling. Thus, nucleolin could be a key factor in glioblastoma pathogenesis and considered a therapeutic target, which may also mediate more signaling pathways.
authors.affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.|Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Shunzeng
authors.initials: S
authors.lastname: Lv
authors.affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.|The First Clinical College of Nanjing Medical University, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Radiotherapy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Glioma Surgery Division, Neurological Surgery Department, Huashan Hospital, Shanghai Medical College of Fudan University, Shanghai, China, 200040.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Zhuang
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: Ruixiang
authors.initials: R
authors.lastname: Bian
authors.affiliation: Glioma Surgery Division, Neurological Surgery Department, Huashan Hospital, Shanghai Medical College of Fudan University, Shanghai, China, 200040. cjyhuashan@163.com.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Yao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000097796:Nucleolin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009687:Nuclear Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D016601:RNA-Binding Proteins; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D000097796:Nucleolin; C082869:CRKL protein