Exploring the Interdependence of TKS4 and CD2AP: Implications for EMT Process and Early Detection in Colon Cancer

Abstract

Colon cancer is a leading cause of death worldwide. Although several molecular biomarkers have been developed for colon cancer, more sensitive and specific methods are needed for its early detection. The TKS4 and CD2AP scaffold proteins have been linked to dynamic actin assembly-related processes, such as cell migration and epithelial-mesenchymal transition (EMT), although their co-instructive role during colon cancer development remains unknown. Therefore, this study was designed to investigate the interdependence of TKS4 and CD2AP during colon cancer progression as well as their involvement in EMT. This is the first study demonstrating a TKS4-CD2AP protein-protein interaction in vitro and in vivo. We describe that CD2AP and TKS4 interdependently induce a mesenchymal transition-like process and impair the migration ability of HCT116 colon cancer cells. Here we show that CD2AP is a novel TKS4 interacting partner, and together they form a scaffold complex that potentially regulates EMT-related signalling. Based on our analysis of the relative TKS4 and CD2AP expression levels, we propose that their levels might cooperatively serve as a reliable biomarker for colon cancer detection.