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The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiology

  • Leaky Junctions in Cancer (Chris Capaldo, Section Editor)
  • Published:
Current Pathobiology Reports

Abstract

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.

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Acknowledgments

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.

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  1. Department of Surgery, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland

    Sri HariKrishna Vellanki, Cathy E. Richards, Yvonne E. Smith & Ann M. Hopkins

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  1. Sri HariKrishna Vellanki
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  2. Cathy E. Richards
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  3. Yvonne E. Smith
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  4. Ann M. Hopkins
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Correspondence to Ann M. Hopkins.

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Sri HariKrishna Vellanki, Cathy E Richards, Yvonne E Smith, and Ann M Hopkins declare that they have no conflict of interest.

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Among cited articles where one of the authors of the current report were authors, local Institutional Review Board approval was obtained and maintained for studies where human (or animal) subjects research was performed.

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This article is part of the Topical Collection on Leaky Junctions in Cancer.

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Vellanki, S.H., Richards, C.E., Smith, Y.E. et al. The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiology. Curr Pathobiol Rep 4, 37–46 (2016). https://doi.org/10.1007/s40139-016-0105-7

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