title: TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways.
abstract: While there were certain studies focusing on the mechanism of TGF-β promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-β may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-β was added, whereas the TGF-β-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significant when the Smad3 was downregulated. Another, the attenuation of TGF-β-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-β addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-β weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-β more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-β and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurology, The Affiliated Taizhou Hospital, Wenzhou Medical University, Taizhou 317000, Zhejiang, China.
authors.forename: Su-zhi
authors.initials: SZ
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
authors.forename: Xiao-pan
authors.initials: XP
authors.lastname: Cao
authors.affiliation: School of Environmental Science and Public Health, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China. Electronic address: wzljm@126.com.
authors.forename: Jia-ming
authors.initials: JM
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009361:Neoplasm Invasiveness; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism*; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: C526007:NODAL protein, human; D055457:Nodal Protein; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ERK1/2; Glioma cell; Nodal; Smad; TGF-β