Cell‐Cell Contact Dependent Subcellular Localization of PAR‐3 Regulated by 14‐3‐3 epsilon

Abstract

14‐3‐3 proteins function as adaptors that regulate multiple signal transduction pathways involved in the cell division, growth, and intracellular trafficking/targeting. Through binding to the phosphoserine motif of the polarity proteins, 14‐3‐3 proteins have been reported to play an important role in conferring cell adhesion and polarization, which are the fundamental processes in cell migration, division and development. In this present study, the roles of the 14‐3‐3ε (PAR‐5) and partitioning defective protein 3 (PAR‐3), a cell‐polarity protein required for establishing cell polarization and apicobasal asymmetries associated with cell adhesion, in the regulation of cancer cell adhesion and polarization was investigated in human hepatocellular carcinoma cells (HCC). Majority of PAR‐3 expression was determined to be localized at the plasma membrane, cytosol and cell‐cell contact interface by immunofluorescent confocal microscopy. The abundant expression of PAR‐3 was subsequently relocated and accumulated to cell‐cell contact while overexpressing 14‐3‐3ε, indicating the vital role of 14‐3‐3ε in regulating function and trafficking of PAR‐3. Moreover, the significant colocalization of PAR‐3 with 14‐3‐3ε and accumulation of catenins‐complex at the cell‐cell contact interface were observed in 14‐3‐3ε overexpressed cells. Molecular interaction of 14‐3‐3ε with PAR‐3 was further confirmed by analysis of protein immunoprecipitation. These results implied that 14‐3‐3ε involved in the modulation of cell polarization and adhesion which may potentially regulate cancer cell metastasis and proliferation.