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      Twist2, the key Twist isoform related to prognosis, promotes invasion of cervical cancer by inducing epithelial-mesenchymal transition and blocking senescence.

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          Abstract

          In response to tumor development, cells initially undergo invasion and metastasis followed by epithelial-mesenchymal transition (EMT, a process by which cells acquire motility) and overriding senescence (an endogenous defense mechanism against tumor progression). Oncogenic activation of Twist1 and Twist2 is essential for EMT and senescence; however, little is known about the specific contributions of Twist1 versus Twist2 to prognosis, metastasis, and the mechanism underlying cervical carcinoma. Here, we investigated the similarities and differences between Twist1 and Twist2 in assessing prognosis and promoting invasion and metastasis of cervical carcinoma as well as their roles in the underlying molecular mechanisms. By monitoring the survival of 144 clinical cervical cancer patients, we demonstrated that Twist2 shows more effective predictive performance compared with Twist1 and is more closely correlated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Compared with Twist1, Twist2 more strongly promotes invasivity and motility by inducing EMT and overriding senescence. Differences between Twist1 and Twist2 in regulating senescence and the cell cycle might be due to their individual roles in regulating the cyclin D1/cyclin dependent kinase 4 (Cdk4) pathway. Overall, our data indicate that Twist2 is the key Twist isoform coupling aberrant signals from EMT to senescence and is an important candidate biomarker for cervical cancer prognosis.

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          Author and article information

          Journal
          Hum. Pathol.
          Human pathology
          1532-8392
          0046-8177
          Sep 2014
          : 45
          : 9
          Affiliations
          [1 ] Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
          [2 ] Department of Gynecologic Oncology, Tumor Hospital of Hubei Provincial, Wuhan, Hubei, 430079, PR China.
          [3 ] Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China. Electronic address: dingma424@yahoo.com.
          [4 ] Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, PR China. Electronic address: smilenn66@126.com.
          [5 ] Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China. Electronic address: sxwang2012@hotmail.com.
          Article
          S0046-8177(14)00205-6
          10.1016/j.humpath.2014.05.001
          24974259
          a6851bc1-74b8-463d-873d-27daa9731b89
          Copyright © 2014 Elsevier Inc. All rights reserved.
          History

          Cervical cancer,Epithelial-mesenchymal transition,Invasion,Prognostic biomarker,Senescence,Twist1,Twist2

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