To achieve strong adhesion to their neighbors and sustain stress and tension, epithelial cells develop many different specialized adhesive structures. Breakdown of these structures occurs during tumor progression with the development of a fibroblastic morphology characteristic of metastatic cells. Adhesion receptors of the Cadherin family have been implicated in these cellular processes, which play an important role in the development and maintenance of the differentiated epithelial phenotype during organogenesis and adult life. Cadherin-mediated adhesion requires the activity of the cytosolic proteins of the Rho subfamily members, Rho, Rac and CDC42 (Cell Division Cycle-42). They belong to the Ras Superfamily of small GTPases, whose function is regulated depending on the type of guanine nucleotide bound. Mammals have three closely related Rac isoforms, Rac1, Rac2 and Rac3 (Ref.1).
References:
1.Role of Rac1 in fibronectin-induced adhesion and motility of human corneal epithelial cells.
Kimura K, Kawamoto K, Teranishi S, Nishida T. Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4323-9. 2.Rac1 and Rac2 regulate macrophage morphology but are not essential for migration. Wheeler AP, Wells CM, Smith SD, Vega FM, Henderson RB, Tybulewicz VL, Ridley AJ. J Cell Sci. 2006 Jul 1;119(Pt 13):2749-57. Epub 2006 Jun 13. 3.Engagement of CD44 promotes Rac activation and CD44 cleavage during tumor cell migration. Murai T, Miyazaki Y, Nishinakamura H, Sugahara KN, Miyauchi T, Sako Y, Yanagida T, Miyasaka M. J Biol Chem. 2004 Feb 6;279(6):4541-50. Epub 2003 Nov 17. 4.Expressions of Rac1, Tiam1 and Cdc42 in retinoblastoma. Adithi M, Venkatesan N, Kandalam M, Biswas J, Krishnakumar S. Exp Eye Res. 2006 Oct 4; 5.WAVE signalling: from biochemistry to biology. Soderling SH, Scott JD. Biochem Soc Trans. 2006 Feb;34(Pt 1):73-6. 6.Rac-1 and IQGAP are potential regulators of E-cadherin-catenin interactions during murine preimplantation development. Natale DR, Watson AJ. Mech Dev. 2002 Dec;119 Suppl 1:S21-6. 7.Activation of ARF6 by ARNO stimulates epithelial cell migration through downstream activation of both Rac1 and phospholipase D. Santy LC, Casanova JE. J Cell Biol. 2001 Aug 6;154(3):599-610. Epub 2001 Jul 30.
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