title: MET receptor is a potential therapeutic target in high grade cervical cancer.
abstract: Cervical cancer is one of the leading causes of death among women suffering from tumors. Current treatment options are insufficient. Here, we investigated the MET receptor as a potential molecular target in advanced cervical cancer. Downregulation of MET receptor expression via RNA interference in different cervical carcinoma cell lines dramatically decreased tumor growth and forced tumor differentiation in vivo. MET receptor silencing also led to a dramatic decrease in cell size and a decrease in proliferation rate under normal and stress conditions. MET receptor downregulation also resulted in decreased cyclin D1 and c-myc levels but did not increase apoptosis. Subsequent experiments showed that downregulation of the MET receptor decreased the expression of a key regulator of the epithelial-to-mesenchymal transition, SLUG. and increased the expression of E-cadherin, a hallmark of the epithelial phenotype. Moreover, MET downregulation impairs expression and signaling of CXCR4 receptor, responsible for invasive phenotype. Taken together, our results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo. These findings highlight a unique role of the MET receptor in cervical carcinoma cells and indicate the MET receptor as a potential therapeutic target for advanced cervical carcinoma.
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Miekus
authors.affiliation: Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Pawlowska
authors.affiliation: Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sekuła
authors.affiliation: Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Drabik
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Madeja
authors.affiliation: Department of Pathomorphology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Adamek
authors.affiliation: Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Majka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006367:HeLa Cells; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C527276:CXCR4 protein, human; D015820:Cadherins; D019718:Receptors, CXCR4; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: CXCR4; E-cadherin; MET; cervical cancer; differentiation