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When over\u2010expressed in a number of cellular systems, these molecules are capable of inhibiting cellular differentiation and anoikis, as well as disrupting cell polarization and tissue architecture, thus increasing tumorigenicity. The present study shows that perturbation of the major fibronectin receptor, integrin \u03b15\u03b21, underlies some of these biological effects. Using confocal microscopy and specific antibodies, CEA and CEACAM6 were demonstrated to co\u2010cluster with integrin \u03b15\u03b21 on the cell surface. The presence of CEA and CEACAM6 was shown to lead to an increase in the binding of the integrin \u03b15\u03b21 receptor to its ligand fibronectin, without changing its cell surface levels, resulting in increased adhesion of CEA\/CEACAM6\u2010expressing cells to fibronectin. More tenacious binding of free fibronectin to cells led to enhanced fibronectin matrix assembly and the formation of a polymerized fibronectin \u201ccocoon\u201d around the cells. Disruption of this process with specific monoclonal antibodies against either fibronectin or integrin \u03b15\u03b21 led to the restoration of cellular differentiation and anoikis in CEA\/CEACAM6 producing cells. J. Cell. Physiol. 210: 757\u2013765, 2007. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.20887","type":"journal-article","created":{"date-parts":[[2006,12,13]],"date-time":"2006-12-13T17:48:12Z","timestamp":1166032092000},"page":"757-765","source":"Crossref","is-referenced-by-count":47,"title":["GPI\u2010anchored CEA family glycoproteins CEA and CEACAM6 mediate their biological effects through enhanced integrin \u03b15\u03b21\u2010fibronectin interaction&amp;"],"prefix":"10.1002","volume":"210","author":[{"given":"Cosme","family":"Ordonez","sequence":"first","affiliation":[]},{"given":"Alexander B.","family":"Zhai","sequence":"additional","affiliation":[]},{"given":"Pilar","family":"Camacho\u2010Leal","sequence":"additional","affiliation":[]},{"given":"Luisa","family":"Demarte","sequence":"additional","affiliation":[]},{"given":"Mannie M.Y.","family":"Fan","sequence":"additional","affiliation":[]},{"given":"Clifford 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