title: TGF-β1/Smad signaling pathway regulates epithelial-to-mesenchymal transition in esophageal squamous cell carcinoma: in vitro and clinical analyses of cell lines and nomadic Kazakh patients from northwest Xinjiang, China.
abstract: Invasion and metastasis are the major causes of death in patients with esophageal squamous cell carcinoma (ESCC). Epithelial-mesenchymal transition (EMT) is a critical step in tumor progression and transforming growth factor-β1 (TGF-β1) signaling has been shown to play an important role in EMT. In this study, we investigated how TGF-β1 signaling pathways contributed to EMT in three ESCC cell lines as well as 100 patients of nomadic ethnic Kazakhs residing in northwest Xinjiang Province of China. In vitro analyses included Western blotting to detect the expression of TGF-β1/Smad and EMT-associated proteins in Eca109, EC9706 and KYSE150 cell lines following stimulation with recombinant TGF-β1 and SB431542, a potent inhibitor of ALK5 that also inhibits TGF-β type II receptor. TGF-β-activated Smad2/3 signaling in EMT was significantly upregulated as indicated by mesenchymal markers of N-cadherin and Vimentin, and in the meantime, epithelial marker, E-cadherin, was markedly downregulated. In contrast, SB431542 addition downregulated the expression of N-cadherin and Vimentin, but upregulated the expression of E-cadherin. Moreover, the TGF-β1-induced EMT promoted invasion capability of Eca109 cells. Tumor cells undergoing EMT acquire fibroblastoid-like phenotype. Expressed levels of TGF-β1/Smad signaling molecules and EMT-associated proteins were examined using immunohistochemical analyses in 100 ESCC tissues of Kazakh patients and 58 matched noncancerous adjacent tissues. The results showed that ESCC tissues exhibited upregulated expression of TGF-β1/Smad. We also analyzed the relationship between the above proteins and the patients' clinicopathological characteristics. The TGF-β1/Smad signaling pathway in human Eca109 ESCC cells may carry similar features as in Kazakh ESCC patients, suggesting that TGF-β1/Smad signaling pathway may be involved in the regulation of EMT in ethnic Kazakh patients with ESCC from Xinjiang, China.
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China; Department of Oncology, People's Hospital of Lianyuan, Lianyuan, Hunan Province, China.
authors.forename: Qiuxiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Cuilei
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Public Health, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Shugang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Clinical Diagnosis Laboratory, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Ju
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Lan
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Hospital of Xingjian Production and Construction Corps, Wulumuqi, Xinjiang, China.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China; Department of Oncology, People's Hospital of Lianyuan, Lianyuan, Hunan Province, China.
authors.forename: Fudong
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pathology, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002681:China; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000208:ethnology / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007623:Kazakhstan; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D014746:Vimentin