title: TGF-β1 inhibits the growth and metastasis of tongue squamous carcinoma cells through Smad4.
abstract: Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that regulates cell growth, differentiation, migration, apoptosis and extracellular matrix remodeling. TGF-β1 transduces signals from the cell membrane to the cell nucleus through serine/threonine kinase receptors and their downstream effectors, Smad molecules. Although many studies have been focused on TGF-β1-Smad signaling pathway, the role of TGF-β1/Smad in tongue squamous cell carcinoma is not fully understood. In the present study, we used a series of cell function assays to examine the role of TGF-β-Smad4 signaling in tongue squamous cell carcinoma. We observed the effects of TGF-β1 on the growth and metastatic potential of the tongue squamous cell carcinoma cell line Ts, which expresses lower level of Smad4 protein. We found that Smad4 could decrease TGF-β1-induced cell proliferation, and that Smad4 overexpression promoted Ts cell apoptosis. In Ts vector control cells, TGF-β1 increased the expression of TβRII, as well as MMP-2, and enhanced cell invasion through the basement membrane, and then induced cell metastasis. However in Ts cells stably expressing Smad4, Smad4 mediated TGF-β1-induced p21 expression promoted cell apoptosis and inhibited cell proliferation, delayed MMP-2 expression, and decreased cell metastasis. Therefore, TGF-β1 plays distinct roles in the Smad4-dependent and -independent signaling pathways.
authors: Department of Dentistry, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. hrbwangmei@yahoo.com.cn
authors: Xiumei
authors: X
authors: Wang
authors: Wenjing
authors: W
authors: Sun
authors: Chengren
authors: C
authors: Zhang
authors: Guohua
authors: G
authors: Ji
authors: Yana
authors: Y
authors: Ge
authors: Ye
authors: Y
authors: Xu
authors: Yuzhen
authors: Y
authors: Zhao
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000235:genetics* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein; D053773:Transforming Growth Factor beta1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2