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Overexpression of TROP2 predicts poor prognosis of patients with cervical cancer and promotes the proliferation and invasion of cervical cancer cells by regulating ERK signaling pathway
- Source :
- PLoS ONE, Vol 8, Iss 9, p e75864 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- Overwhelming evidence has demonstrated that the aberrant expression of the human trophoblast cell-surface antigen (TROP2) was associated with tumor aggressiveness and poor prognosis in a variety of human cancers, however the roles of TROP2 in cervical cancer have not been investigated. The purpose of our study was to elucidate the prognostic significance of TROP2 expression in patients with cervical cancer and determine its effect on tumor progression. Immunohistochemistry assay showed that 88.7% (94/106 cases) of cervical cancer specimens were positively stained with TROP2, and the overexpression of TROP2 was closely related with FIGO stage, histological grades, lymphatic metastasis, invasive interstitial depth and high expression of Ki-67. Patients with TROP2-positive staining exhibited a significantly decreased overall survival and progression free survival; it was also an independent predictor for prognosis according to multivariate analysis. Moreover, down-regulation of TROP2 mediated by siRNA in Siha and CaSki cells resulted in a strong inhibition of proliferation and invasion, TROP2 abrogation also elevated the apoptotic ratio and caused G1 arrest. Conversely, enforced expression of TROP2 in HeLa and C33A cells remarkably promoted cell growth, migration and invasion. In addition, the tumorigenic function of TROP2 was associated with the increased expressions of cyclin D1, cyclin E, CDK2 and CDK4 but reduced expression of p27 and E-cadherin via the activation of Erk1/2 signaling pathway. Furthermore, the inhibition of TROP2 expression in cervical cancer cell lines enhances sensitivity to cisplatin. The present study suggest that overexpression of TROP2 may play crucial roles in the development and pathogenesis of human cervical cancer, therefore, TROP2 may represent a prospective prognostic indicator and a potential therapeutic target of cervical cancer.
- Subjects :
- Pathology
medicine.medical_specialty
Cyclin E
MAP Kinase Signaling System
Blotting, Western
Fluorescent Antibody Technique
Uterine Cervical Neoplasms
lcsh:Medicine
Biology
Metastasis
HeLa
Cyclin D1
Antigens, Neoplasm
Cell Line, Tumor
medicine
Humans
Neoplasm Invasiveness
RNA, Small Interfering
lcsh:Science
Cell Proliferation
Cervical cancer
Cisplatin
Analysis of Variance
Multidisciplinary
Cell growth
lcsh:R
Flow Cytometry
Prognosis
medicine.disease
biology.organism_classification
Immunohistochemistry
Gene Expression Regulation, Neoplastic
Ki-67 Antigen
Tumor progression
Bisbenzimidazole
Cancer research
Female
lcsh:Q
Cell Adhesion Molecules
Research Article
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....8db3d16139f5ce1fed05c360921113b1