Adherens junction, Adhesion, Adhesion molecules, Apical junctional complex, Barrier function, Cancer, Cell migration, Cell-cell, Cell-matrix, Crosstalk, Epithelial, Extracellular matrix, GTPases, Pathogens, Rho, Tight junction, Tyrosine kinases.
Supported by Past and present funding in the senior author’s laboratory as follows - Health Research Board of Ireland (HRA-POR-2014-545; HRA/2009/49; RP/2006/95, to Hopkins AM); Science Foundation Ireland (13/IA/1994; 2008/RFP/NSC1427; 2008/RFP/NSC1427 TIDA Feasibility 10, to Hopkins AM); Cancer Research Ireland, Breast Cancer Ireland; Brazil Science Without Borders (CAPES-13306-13-8) and the Beaumont Hospital Cancer Research and Development Trust.
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.
Medicine and Health Sciences | Surgery
Smith YE, Vellanki SH, Hopkins AM. Dynamic interplay between adhesion surfaces in carcinomas: Cell-cell and cell-matrix crosstalk. World Journal of Biological Chemistry. 2016;7(1):64-77.
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