Dynamic interplay between adhesion surfaces in carcinomas: Cell-cell and cell-matrix crosstalk

Abstract

Cell-cell and cell-matrix signaling and communication between adhesion sites involve mechanisms which are required for cellular functions during normal development and homeostasis; however these cellular functions and mechanisms are often deregulated in cancer. Aberrant signaling at cell-cell and cell-matrix adhesion sites often involves downstream mediators including Rho GTPases and tyrosine kinases. This review discusses these molecules as putative mediators of cellular crosstalk between cell-cell and cell-matrix adhesion sites, in addition to their attractiveness as therapeutic targets in cancer. Interestingly, inter-junctional crosstalk mechanisms are frequently typified by the way in which bacterial and viral pathogens opportunistically infect or intoxicate mammalian cells. This review therefore also discusses the concept of learning from pathogen-host interaction studies to better understand coordinated communication between cell-cell and cell-matrix adhesion sites, in addition to highlighting the potential therapeutic usefulness of exploiting pathogens or their products to tap into inter-junctional crosstalk. Taken together, we feel that increased knowledge around mechanisms of cell-cell and cell-matrix adhesion site crosstalk and consequently a greater understanding of their therapeutic targeting offers a unique opportunity to contribute to the emerging molecular revolution in cancer biology.

Keywords: Cell-cell; Cell-matrix; Adhesion; Cancer; Crosstalk; Pathogens; Epithelial; Barrier function; Tight junction; Cell migration; Apical junctional complex; Adherens junction; Adhesion molecules; Extracellular matrix; Tyrosine kinases; GTPases; Rho

Core tip: Deregulation of cell-cell and cell-matrix signaling makes well-established contributions to key elements of cancer initiation and progression. In this review we discuss mechanisms of crosstalk between these spatially-distinct adhesion sites in epithelial cells, with a view to understanding their therapeutic targeting in epithelial tumors (carcinomas). A particular focus is placed upon Rho GTPases and tyrosine kinases as mediators of inter-junctional crosstalk, in addition to the concept of opportunistic pathogenic infection as a paradigm for inter-junctional crosstalk. Overall, this review posits that a greater understanding of cell-cell and cell-matrix adhesion crosstalk will drive novel aspects of cancer drug discovery.