How are cell-cell adhesions regulated?2017-12-26T12:42:34+00:00

How are cell-cell adhesions regulated?

Introduction to the regulation of cell-cell adhesion

The assembly and disassembly of cell-cell junctions, such as adherens junctions (AJ), are regulated by a vast array of factors functioning in a highly complex network of molecular switches and mechanical cues. Although adhesion complexes are often transient, effective regulation of their assembly and disassembly is crucial for regular cell function. This is evidenced by the fact that destabilization of AJ dynamics has been correlated to the onset of cancer cell metastasis where increased cell motility and invasion is commonly observed [1]. Indeed, one recent study attributed the oncosuppressive properties of the RhoGAP protein DLC1 (deleted in liver cancer 1) to a role in the stabilization of AJs [2].

With AJs essentially being a functional extension of the cytoskeleton, their formation and stability is heavily dependent on that of the actin filament network. Regulation of the adhesion complex is maintained by a combination of actin cytoskeleton dynamics, the influence of AJ scaffolding proteins, and the effect of post-translational modification of AJ components. Each protein involved in the regulation of the adhesion complex must first be recruited to the complex, and in most cases, must be activated in order to carry out their function. Thus, regulation of the adhesion complex is a highly complicated system involving several independent molecular pathways [3]. Efforts to dissect each regulatory mechanism are therefore ongoing and many interactions and consequences are still unknown.

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References

  1. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer 2002; 2(6):442-54. [PMID: 12189386]
  2. Tripathi V, Popescu NC, and Zimonjic DB. DLC1 interaction with α-catenin stabilizes adherens junctions and enhances DLC1 antioncogenic activity. Mol. Cell. Biol. 2012; 32(11):2145-59. [PMID: 22473989]
  3. Zaidel-Bar R. Cadherin adhesome at a glance. J. Cell. Sci. 2013; 126(Pt 2):373-8. [PMID: 23547085]