title: Correlation of Twist upregulation and senescence bypass during the progression and metastasis of cervical cancer.
abstract: Cervical carcinoma is associated with high propensity for local invasion and lymph node metastasis. However, the molecular alterations that drive progression and metastasis of cervical cancer remain unclear. Cellular senescence has been proposed as the mechanism that protects an organism against cancer progression and metastasis. In addition, Twist, a basic helix-loop-helix transcription factor, has been suggested as an oncogene because it is overexpressed in many types of human cancer. This gene also exhibits a positive function in regulating invasion and metastasis. In this study, Twist was strongly and positively expressed in normal tissue, squamous cell carcinoma (SCC) IA-IIA, and SCC IIB-IIIB (4.3%, 44%, and 88.9%, respectively). The strong positive expressions of the senescence marker CBX3 were 39.1%, 32%, and 15.6%, respectively. The strong positive expressions of Twist in the SCC groups with or without lymph node metastasis were 80.8% and 50%. For CBX3, such expressions were 7.7% and 29.5%, respectively. Results also showed that the expression of Twist was inversely correlated with that of CBX3. Moreover, the knockdown of Twist with target siRNA in SiHa triggered the induction of the chromatin marker of the cellular senescence CBX3 and senescence-associated β-galactosidase activity. Our results suggested that the expression of Twist increased during the progression and metastasis of cervical cancer. Furthermore, Twist-induced senescence bypass is important in this process.
authors.affiliation: Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Abidan
authors.initials: A
authors.lastname: Tuerhanjiang
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.forename: Zhangying
authors.initials: Z
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Yuan
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
mesh_terms: D000354:Africa, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D016922:Cellular Senescence / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000502:physiology; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D009362:Neoplasm Metastasis / Q000473:pathology / Q000503:physiopathology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D051879:Twist-Related Protein 1 / Q000096:biosynthesis / Q000502:physiology*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C518294:CBX3 protein, human; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1