The Molecular Aspects of Tight Junctions

Tight junctions (TJs) are multi-protein complexes whose principal function is to mediate cell-cell adhesion between epithelial or endothelial cells. While once thought to participate solely as passive effectors of adhesion, it is increasingly being recognised that TJs are dynamic structures which regulate many aspects of cellular function and physiology. Accordingly, dysregulation of TJ-based adhesion or signalling is emerging as an intriguing contributor to several pathophysiologies including cancer. This review will attempt to summarise the current state of knowledge about molecular aspects which regulate, and are regulated by, TJs. The first section will outline selected physiological processes known to influence TJ structure or function, under the headings of cell adhesion/polarity, cell-matrix signalling, ion transport, hormone effects, pro-inflammatory cytokines and hypoxia. The second section will describe selected functional behaviours within the pathophysiology of cancer which TJs have been demonstrated to influence, encompassing cell proliferation and apoptosis, migration and invasion, cell fate and differentiation, metastasis across the blood brain barrier and finally angiogenesis. Collectively, these sections illustrate that a wealth of mechanistic information can be gained from interrogating the contribution of TJs to normal physiology. In turn they highlight how TJ-based disturbances can promote some of the functional behaviours associated with cancer, and thereby offer insight into new TJ-based targets that may offer pharmacological promise in halting tumour progression.