MP31-13 THE EXPRESSION AND FUNCTION OF FAM110A IN HUMAN PROSTATE CANCER

Abstract

INTRODUCTION AND OBJECTIVES: The loss of cell-cell contacts between epithelial cells is an important step in cancer progression. Alpha-catenin plays a crucial role in E-cadherin mediated cell-cell adhesion. We identified a novel protein FAM110A that interacts with alpha-catenin. FAM110A is a member of FAM110 gene family that was originally identified in a search for centrosome and spindle pole-associated proteins, but whose function in cancer is still unknown. We hypothesized that FAM110A plays a role in prostate cancer (PrCa) progression. The objective of this study is to analyze the expression and biological functions of FAM110A in PrCa. METHODS: Expression of the FAM110A gene in tumor cell lines and in human PrCa tissues was analyzed by quantitative real-time PCR. We created an EGFP-tagged FAM110A expression vector to observe the localization of FAM110A in cancer cells. Co-immunoprecipitation experiments were performed to confirm the genuine interaction between FAM110A and alpha-catenin. We established a doxycycline-inducible FAM110A expressing A431 cell line. This cell line was used to study the effect of FAM110A on cell viability, migration and invasion, using CellTiter-Glo , wound healing and Matrigel invasion assays, respectively. RESULTS: In human prostate tissues, we found that FAM110A mRNA expression in primary PrCa was unchanged, but was significantly increased in PrCa metastasis (1.5-fold increase compared to normal prostate tissue, p1⁄40.037). The immunofluorescence staining showed that FAM110A was co-localized with E-cadherin and betacatenin at cell-cell adherence junctions. In doxycycline-inducible FAM110A cells, FAM110A did neither affect cell viability nor cell migration, but cell invasiveness was significantly increased after FAM110A induction (1.9-fold compared to non-induced cells, p1⁄40.002). FAM110A expressing cells had a more spindle-like cell morphology, and had impaired F-actin bundle formation. CONCLUSIONS: FAM110A gene expression analysis in prostate tissues suggests that FAM110A plays a role in PrCa metastasis. Furthermore, results of functional assays indicate that binding of FAM110A to alpha-catenin may change the interaction between alpha-catenin and the actin cytoskeleton, which results in a more mesenchymal-like cell morphology and the acquisition of an invasive phenotype.