title: Lefty inhibits glioma growth by suppressing Nodal-activated Smad and ERK1/2 pathways.
abstract: As a common malignant tumor, glioma has long been a refractory disease in the field of neurosurgery. Exploration of its etiology, pathogenesis, biological characteristics, and new treatment measures is a hot topic as well as a problem most difficult to solve in the neurosurgical division. In recent years, the role of Nodal and its feedback inhibitor Lefty in tumors has drawn more and more attention and may form a new target for cancer therapy. Western blot detection indicated that there was almost no expression of Lefty protein in glioma cells. Transfection of Lefty-overexpressing vector into GBM8401 and GBM glioma cells significantly decreased the expression of Nodal. Nodal can significantly increase the phosphorylation levels of Smad2 and Smad3 and activate the ERK1/2 pathway; meanwhile, Nodal promotes the proliferation and invasion of glioma cells and inhibits their apoptosis. However, when cells were co-transfected with both Lefty- and Nodal-overexpressing vectors, Lefty inhibited the above effects of Nodal in glioma cells, hence significantly reduced the levels of phosphorylated Smad2, Smad3, and ERK1/2, inhibited the proliferation and invasion of glioma cells, and increased their apoptosis. These results indicate that in glioma cells, Lefty inhibits Nodal-mediated activation of Smad and ERK1/2 signaling pathways, thereby suppressing the promoting effect of Nodal on tumor growth.
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Yancheng Affiliated with Nantong University, Yancheng 224001, PR China.
authors.forename: Guan
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou 215300, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Jiangning Hospital Affiliated with Nanjing Medical University, Nanjing 211100, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Yancheng Affiliated with Nantong University, Yancheng 224001, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Yancheng Affiliated with Nantong University, Yancheng 224001, PR China.
authors.forename: Linshan
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Yancheng Affiliated with Nantong University, Yancheng 224001, PR China. Electronic address: junguo8916@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002460:Cell Line; D005910:Glioma / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D055458:Left-Right Determination Factors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D055457:Nodal Protein / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D014162:Transfection
chemical_list: D055458:Left-Right Determination Factors; D055457:Nodal Protein; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein
keywords: ERK1/2; Glioma; Lefty; Nodal; Smad; Tumor