Abstract 2027: CBX7 protein, whose expression is decreased in human carcinomas, positively regulates E-cadherin expression by interacting with the HDAC2 protein

Abstract

Abstract CBX7 is a chromobox family protein encoding a novel Polycomb protein whose expression shows a progressive reduction, well related with the malignant grade of the thyroid neoplasias. Indeed, CBX7 protein levels decreased in an increasing percentage of cases going from benign adenomas to papillary, follicular and anaplastic thyroid carcinomas. To elucidate the function of CBX7 in carcinogenesis, we searched for CBX7 interacting proteins by a proteomic analysis. By this approach, we identified several proteins among which we selected Histone deacetylase 2 that is well known to play a key role in neoplastic cell transformation and to downregulate E-cadherin expression, whose loss is a critical event in the Epithelial-Mesenchymal Transition (EMT). We confirmed by co-immunoprecipitation that CBX7 physically interacts with the Histone deacetylase 2 protein and is able to inhibit its activity. Then, we showed that both these proteins bind the E-cadherin promoter, and that CBX7 is able to upregulate E-cadherin expression. Consistent with these data we found a positive statistical correlation between CBX7 and E-cadherin expression in human thyroid carcinomas. Finally, we demonstrated that the expression of CBX7 increases the acetylation status of the histones H3 and H4 on the E-cadherin promoter. Therefore, the ability of CBX7 to positively regulate E-cadherin expression by interacting with Histone deacetylase 2 and inhibiting its activity on the E-cadherin promoter would account for the correlation between the loss of CBX7 expression and a highly malignant phenotype in thyroid cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2027. doi:10.1158/1538-7445.AM2011-2027