RhoGTPase signalling at epithelial tight junctions: Bridging the GAP between polarity and cancer

The International Journal of Biochemistry & Cell Biology
Ceniz Zihni, Stephen James Terry

Abstract

The establishment and maintenance of epithelial polarity must be correctly controlled for normal development and homeostasis. Tight junctions (TJ) in vertebrates define apical and basolateral membrane domains in polarized epithelia via bi-directional, complex signalling pathways between TJ themselves and the cytoskeleton they are associated with. RhoGTPases are central to these processes and evidence suggests that their regulation is coordinated by interactions between GEFs and GAPs with junctional, cytoplasmic adapter proteins. In this InFocus review we determine that the expression, localization or stability of a variety of these adaptor proteins is altered in various cancers, potentially representing an important mechanistic link between loss of polarity and cancer. We focus here, on two well characterized RhoGTPases Cdc42 and RhoA who's GEFs and GAPs are predominantly localized to TJ via cytoplasmic adaptor proteins.

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Citations

Feb 24, 2018·Physical Biology·Cole ZmurchokLeah Edelstein-Keshet
Apr 30, 2017·World Journal of Gastrointestinal Oncology·Zheng-Yun LiangWen-Xian Guan
Feb 1, 2020·The Journal of Cell Biology·Aaron P van LoonAlvaro Sagasti
Jun 21, 2020·Biochimica Et Biophysica Acta. Biomembranes·Covadonga Díaz-DíazFernando Martín-Belmonte
Jul 25, 2021·International Journal of Molecular Sciences·Ashley MonacoKurt Amsler
Oct 19, 2017·Current Opinion in Systems Biology·Wouter-Jan Rappel, Leah Edelstein-Keshet

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BETA
nucleotide exchange
nuclear translocation

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