TGF-β1/Smad Signaling Pathway Regulates Epithelial To Mesenchymal Transition In Kazakh Esophageal Squamous Cell Carcinoma

Objective: To investigate the effect and mechanism of TGF-β1/Smad signaling pathway in esophagealsquamous cell carcinoma epithelial-mesenchymal transition (EMT); On the basis of the cytologicalexperiments, then to explore TGF-β1/Smad signaling pathway proteins and EMT-related protein expressionand analyze its relationship with clinical and pathological features in Kazakh esophageal carcinoma. Wefurther aimed to investigate TGF-β1/Smad signaling was involved in the regulation of EMT and lay thefoundation for the development of the mechanism in Kazakh esophageal squamous cell carcinoma (ESCC),and to provide a theoretical basis of therapy and tumor’s infiltration and metastasis.Methods: Different concentrations of TGFβ1and SB431542were dealed with Eca109, Western blottingwas performed to detect the expression of TGF-β1/Smad signaling and EMT-associated proteins of humanesophageal carcinoma cell line Ec109induced by TGF-β1and inhibited by SB431542in the differentcondition; Transwell assay was used to estimate TGF-β1-induced invasion and metastasis; Then100formalin-fixed，paraffin-embedded cases of ESCC and58non-cancerous adjacent tissue (NCAT) wereexamined the expression of TGF-β1/Smad signaling and EMT-associated proteins byimmunohistochemistry using tissue microarray. The associations between expression of TGF-β1/Smadsignaling and EMT-associated proteins with clinicopathologic parameters were analyzed.Results: TGF-β1can induce Eca109cells morphological changes and increase migration and invasion.The proteins of N-cadherin、Vimentin、Smad2/3and Smad4expression were up-regulated with TGF-β1treated by Western blotting, but Smad7was down-regulated. while with SB431542treated the cell, theresults showed the protein levels of Vimentin、Smad2/3and Smad4were down-regulated, the protein levelsof Smad7was up-regulated. The positive expression rates of TGF-β1、p-Smad2/3、N-cadherin and Vimentinin the esophageal squamous cell carcinoma tissues was significantly higher than the non-cancerous adjacenttissue cases expression (p<0.001), while the positive expression rates of E-cadherin in the esophagealsquamous cell carcinoma tissues was significantly lower than the non-cancerous adjacent tissue casesexpression (p<0.001), the expression of TGF-β1had a positive correlation with p-Smad2/3(r=0.186,p=0.064)、N-cadherin (r=0.321, p<0.001) and Vimentin (r=0.113, p=0.265), a negative correlation withE-cadherin (r=－0.123, p=0.027).Conclusions:1. TGF-β1/Smad signal transduction pathway mediates EMT process in human esophagealcarcinoma cell line Eca109;2. Overexpression of TGF-β1、p-Smad2/3in ESCC; In ESCC, negativecorrelations between the expression of TGF-β1and E-cadherin，and positively corrletated between theexpression of TGF-β1and N-cadherin, TGF-β1/Smad signal transduction pathway may be involved in theregulation of EMT in carcinogenesis and development of XinJiang Kazakh esophageal squamous cellcarcinoma.