title: Twist induces epithelial-mesenchymal transition in cervical carcinogenesis by regulating the TGF-β/Smad3 signaling pathway.
abstract: Epithelial-mesenchymal transition (EMT) is associated with the metastasis and poor prognosis of cervical cancer. However, the underlying mechanisms are poorly defined. In the present study, we investigated whether Twist plays a direct role in human cervical cancer using immunohistochemical and western blot analyses. Immunohistochemical analysis revealed that Twist is highly expressed in cervical cancer, which correlates with poor tumor pathological differentiation or lymph node metastasis (P<0.05). Depletion of Twist by stable shRNA-mediated knockdown decreased the migratory ability of cancer cell lines in vitro. Suppression or overexpression of Twist also resulted in an altered expression of the molecular mediators of EMT. Furthermore, exogenous TGF-β promoted EMT by upregulating the expression of Twist through the TGF-β/Smad3 pathway, and this effect was eliminated by Twist depletion in cancer cells as demonstrated in the in vitro study. The use of in vivo models revealed a decreased tumor proliferation potential in Twist-depleted cancer cells. The results suggested a novel function for Twist in the promotion of EMT via TGF-β/Smad3 signaling pathway. Thus, Twist constitutes a potential therapeutic target in human cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Mei-Ting
authors.initials: MT
authors.lastname: Qiu
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Zhou
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Limo
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Zhu-Nan
authors.initials: ZN
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bao
mesh_terms: D063646:Carcinogenesis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D051879:Twist-Related Protein 1