title: Twist2, the key Twist isoform related to prognosis, promotes invasion of cervical cancer by inducing epithelial-mesenchymal transition and blocking senescence.
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.
authors: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors: Tian
authors: T
authors: Wang
authors: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors: Yan
authors: Y
authors: Li
authors: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors: Wenwen
authors: W
authors: Wang
authors: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors: Abidan
authors: A
authors: Tuerhanjiang
authors: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors: Zhangying
authors: Z
authors: Wu
authors: Department of Gynecologic Oncology, Tumor Hospital of Hubei Provincial, Wuhan, Hubei, 430079, PR China.
authors: Runfeng
authors: R
authors: Yang
authors: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors: Ming
authors: M
authors: Yuan
authors: 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.
authors: Ding
authors: D
authors: Ma
authors: Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, PR China. Electronic address: smilenn66@126.com.
authors: Wei
authors: W
authors: Wang
authors: 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.
authors: Shixuan
authors: S
authors: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D002465:Cell Movement; D016922:Cellular Senescence; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms; D012372:ROC Curve; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; C530104:CCND1 protein, human; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins; C103173:TWIST1 protein, human; C486274:TWIST2 protein, human; D051879:Twist-Related Protein 1; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: Cervical cancer; Epithelial-mesenchymal transition; Invasion; Prognostic biomarker; Senescence; Twist1; Twist2