Abstract:
:Expression of the tight junction protein junctional adhesion molecule-A (JAM-A) has been linked to proliferation and tumour progression. However, a direct role for JAM-A in regulating proliferative processes has not been shown. By using complementary in vivo and in vitro approaches, we demonstrate that JAM-A restricts intestinal epithelial cell (IEC) proliferation in a dimerization-dependent manner, by inhibiting Akt-dependent β-catenin activation. Furthermore, IECs from transgenic JAM-A(-/-)/β-catenin/T-cell factor reporter mice showed enhanced β-catenin-dependent transcription. Finally, inhibition of Akt reversed colonic crypt hyperproliferation in JAM-A-deficient mice. These data establish a new link between JAM-A and IEC homeostasis.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Nava P,Capaldo CT,Koch S,Kolegraff K,Rankin CR,Farkas AE,Feasel ME,Li L,Addis C,Parkos CA,Nusrat Adoi
10.1038/embor.2011.16subject
Has Abstractpub_date
2011-04-01 00:00:00pages
314-20issue
4eissn
1469-221Xissn
1469-3178pii
embor201116journal_volume
12pub_type
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