BACKGROUND: The prognosis of the oral squamous cell carcinoma (OSCC) patients remains very poor, mainly due to their high propensity to invade and metastasize. E-cadherin reduced expression occurs in the primary step of oral tumour progression and gene methylation is a mode by which the expression of this protein is regulated in cancers. In this perspective, we investigated E-cadherin gene (CDH1) promoter methylation status in OSCC and its correlation with Ecadherin protein expression, clinicopathological characteristics and patient outcome. METHODS: Histologically proven OSCC and paired normal mucosa were analyzed for CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction and immunohistochemistry. Colocalization of E-cadherin with epidermal growth factor (EGF) receptor (EGFR) was evidenced by confocal microscopy and by immunoprecipitation analyses. RESULTS: This study indicated E-cadherin protein down-regulation in OSCC associated with protein delocalization from membrane to cytoplasm. Low E-cadherin expression correlated to aggressive, poorly differentiated, high grade carcinomas and low patient survival. Moreover, protein down-regulation appeared to be due to E-cadherin mRNA downregulation and CDH1 promoter hypermethylation. In an in vitro model of OSCC the treatment with EGF caused internalization and co-localization of E-cadherin with EGFR and the addition of demethylating agents increased E-cadherin expression. CONCLUSION: Low E-Cadherin expression is a negative prognostic factor of OSCC and is likely due to the hypermethylation of CDH1 promoter. The delocalization of E-cadherin from membrane to cytoplasm could be also due to the increased expression of EGFR in OSCC and the consequent increase of E-cadherin co-internalization with EGFR.
BACKGROUND: The prognosis of the oral squamous cell carcinoma (OSCC) patients remains very poor, mainly due to their high propensity to invade and metastasize. E-cadherin reduced expression occurs in the primary step of oral tumour progression and gene methylation is a mode by which the expression of this protein is regulated in cancers. In this perspective, we investigated E-cadherin gene (CDH1) promoter methylation status in OSCC and its correlation with Ecadherin protein expression, clinicopathological characteristics and patient outcome. METHODS: Histologically proven OSCC and paired normal mucosa were analyzed for CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction and immunohistochemistry. Colocalization of E-cadherin with epidermal growth factor (EGF) receptor (EGFR) was evidenced by confocal microscopy and by immunoprecipitation analyses. RESULTS: This study indicated E-cadherin protein down-regulation in OSCC associated with protein delocalization from membrane to cytoplasm. Low E-cadherin expression correlated to aggressive, poorly differentiated, high grade carcinomas and low patient survival. Moreover, protein down-regulation appeared to be due to E-cadherin mRNA downregulation and CDH1 promoter hypermethylation. In an in vitro model of OSCC the treatment with EGF caused internalization and co-localization of E-cadherin with EGFR and the addition of demethylating agents increased E-cadherin expression. CONCLUSION: Low E-Cadherin expression is a negative prognostic factor of OSCC and is likely due to the hypermethylation of CDH1 promoter. The delocalization of E-cadherin from membrane to cytoplasm could be also due to the increased expression of EGFR in OSCC and the consequent increase of E-cadherin co-internalization with EGFR.
Authors: Petros Papagerakis; Giuseppe Pannone; L I Zheng; Maria Athanassiou-Papaefthymiou; Yashuo Yamakoshi; Howard Stan McGuff; Omar Shkeir; Konstantinos Ghirtis; Silvana Papagerakis Journal: Anticancer Res Date: 2015-04 Impact factor: 2.480
Authors: Giuseppe Pannone; Riccardo Nocini; Angela Santoro; Francesca Spirito; Pier Francesco Nocini; Silvana Papagerakis; Renny T Franceschi; Marina Di Domenico; Angelina Di Carlo; Nana Danelia; Lorenzo Lo Muzio Journal: Biomolecules Date: 2022-04-16
Authors: Maurizio Romano; Francesco De Francesco; Giuseppe Pirozzi; Enrico Gringeri; Riccardo Boetto; Marina Di Domenico; Barbara Zavan; Giuseppe A Ferraro; Umberto Cillo Journal: Oncoscience Date: 2015-05-15
Authors: Angela Santoro; Giuseppe Pannone; Silvana Papagerakis; H Stan McGuff; Barbara Cafarelli; Silvia Lepore; Salvatore De Maria; Corrado Rubini; Marilena Mattoni; Stefania Staibano; Ernesto Mezza; Gaetano De Rosa; Gabriella Aquino; Simona Losito; Carla Loreto; Salvatore Crimi; Pantaleo Bufo; Lorenzo Lo Muzio Journal: Biomed Res Int Date: 2014-01-08 Impact factor: 3.411