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.