Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Feb 26, 2016; 7(1): 64-77
Published online Feb 26, 2016. doi: 10.4331/wjbc.v7.i1.64
Dynamic interplay between adhesion surfaces in carcinomas: Cell-cell and cell-matrix crosstalk
Yvonne E Smith, Sri HariKrishna Vellanki, Ann M Hopkins
Yvonne E Smith, Sri HariKrishna Vellanki, Ann M Hopkins, Department of Surgery, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland
Author contributions: Smith YE contributed to designing the aims of the review, contributed to writing the manuscript and generated the figure; Vellanki SH contributed to writing the manuscript; Hopkins AM designed the aims of the review, contributed to writing the manuscript and reviewed the manuscript.
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.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ann M Hopkins, PhD, Department of Surgery, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland. annhopkins@rcsi.ie
Telephone: +353-1-8093858 Fax: +353-1-6335082
Received: June 9, 2015
Peer-review started: June 11, 2015
First decision: August 25, 2015
Revised: September 22, 2015
Accepted: November 3, 2015
Article in press: November 4, 2015
Published online: February 26, 2016
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.