The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiology.
The epithelial linings of eukaryotic organs form dynamically-regulated selectively-permeable barriers that control the movement of substances into (and out of) mucosal tissues. The principal structural determinants of epithelial barrier function are intercellular tight junctions (TJs), multi-protein complexes composed of claudin and non-claudin transmembrane proteins in addition to cytosolic linker proteins. As well as their crucial roles in barrier function, it is now well recognized that TJ proteins coordinate a variety of signaling and trafficking functions regulating physiological events such as cell differentiation, proliferation, migration and polarity. Accordingly, dysregulations in TJ protein expression or function are increasingly being linked to several pathophysiologies including cancer. To date, claudins have received the most attention as putative contributors to cancer initiation or progression. However the contribution of non-claudin transmembrane TJ proteins (including select immunoglobulin superfamily members, nectins, occludin and Marvel D family members) to the pathophysiology of cancer remains incompletely understood. Therefore the focus of this review is to collate recently-published evidence that supports or discounts a role for non-claudin transmembrane TJ proteins in cancer, and to speculate upon the feasibility of these molecules as prognostic biomarkers or therapeutic targets in cancer.
We thank current and former members of the Hopkins laboratory for their hard work and helpful discussions, and are grateful to the following funding agencies for support in recent years: Science Foundation Ireland (13/IA/1994; 2008/RFP/NSC1427; 2008/RFP/NSC1427 TIDA Feasibility 10, to AMH); Health Research Board of Ireland (HRA POR-2014-545; HRA/2009/49; RP/2006/95, to AMH); Breast Cancer Ireland; The Beaumont Hospital Cancer Research and Development Trust.
CommentsThis is a post-peer-review, pre-copyedit version of an article published in Current Pathology Reports. The final authenticated version is available online at: https://doi.org/10.1007/s40139-016-0105-7
Published CitationVellanki SH, Richards CE, Smith YE, Hopkins AM. The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiolog. Current Pathology Reports 2016;(2):37-46.
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