title: TGF-β1 mediates epithelial to mesenchymal transition via the TGF-β/Smad pathway in squamous cell carcinoma of the head and neck.
abstract: Development of metastasis is a major cause of death for squamous cell carcinoma of the head and neck (SCCHN) patients. Epithelial to mesenchymal transition (EMT) is now regarded as a correlate of tumor metastasis. Given that transforming growth factor-β1 (TGF-β1) is an important inducer of EMT, we examined the effects of TGF-β1 on the human SCCHN cell line Tu686. We found that TGF-β1 mediated cell morphological changes. Phase-contrast microscopy revealed a loss of the adherent phenotype with cellular elongation, decrease in cell-to-cell contact, and the induction of a fibroblast-like state. Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that TGF-β1 could induce down-regulation of the epithelial marker E-cadherin and up-regulation of the mesenchymal marker vimentin in Tu686 cells in a concentration- and time-dependent manner. Wound- healing and transwell invasion assay indicated that TGF-β1 promoted Tu686 cell migration and invasion dramatically. In addition, these changes were mediated via canonical TGF-β/Smad signaling with concomitant up-regulation of phosphorylated Smad2. Smad2 RNAi abrogated both expression and functional effects of TGF-β1 on Tu686 cells. In conclusion, the present study demonstrates that TGF-β1 could induce EMT in the SCCHN cell line via the TGF-β/Smad signaling pathway. More importantly, a cell model for EMT was established, which is valuable for future studies on the metastasis of SCCHN.
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, PR China.
authors.forename: Changyun
authors.initials: C
authors.lastname: Yu
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Donghai
authors.initials: D
authors.lastname: Huang
authors.forename: Yaozhang
authors.initials: Y
authors.lastname: Dai
authors.forename: Gengming
authors.initials: G
authors.lastname: Cai
authors.forename: Jinjie
authors.initials: J
authors.lastname: Sun
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Tian
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D053773:Transforming Growth Factor beta1