Insights into the Dynamics of Focal Adhesion Protein Trafficking in Invasive Cancer Cells and Clinical Implications

Abstract

AbstractThe development of cancer metastases is multifactorial and can be affected by a wide range of host, cell, and tissue-microenvironment factors. A crucial cellular event by which primary cancer cells invade neighboring tissue structures and distant organs involves the acquisition of autonomous motile and invasive properties; these can be inherent to a specific cancer cell variant, possibly cancer stem-cell type, or can be acquired during the course of tumor progression. Several transmembrane receptors, focal contact proteins, cell cytoskeleton and motor proteins, and intracellular signaling molecules converge to regulate cell migration and invasion. In particular, great research efforts have pinpointed the central role of focal adhesion dynamics and turnover within distinct subcellular compartments in the regulation of cell traction and retraction forces that drive, essential cell locomotion and invasion of neighboring tissues. Of clinical relevance, several components of the signaling pathways that regulate focal adhesion trafficking and turnover are deregulated in human cancer tissues; overexpression and hyperactivation are more common in invasive cancers compared to benign disease. This chapter provides the reader with an abridged, updated, and clinically relevant overview of signaling pathways that regulate trafficking and turnover of focal adhesion proteins involved in cancer cell migration and invasion. Potential clinical implications of specific proteins that can be exploited as biomarkers and therapeutic targets for the management of metastatic disease are emphasized. For detailed molecular biology of trafficking signaling, we refer the reader to selected seminal reviews in the field.KeywordsIntegrin focal adhesionTraffickingMigrationInvasion