Epithelial Pathobiology Research Unit, Department of Pathology, Emory University, Whitehead Biomedical Research Building, Room 105E, 615 Michael Street, Atlanta, Georgia 30322, USA.
EMBO Rep. 2011 Apr;12(4):314-20. doi: 10.1038/embor.2011.16. Epub 2011 Mar 4.
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.
紧密连接蛋白连接黏附分子-A（JAM-A）的表达与增殖和肿瘤进展有关。然而，JAM-A 在调节增殖过程中的直接作用尚未得到证实。通过使用互补的体内和体外方法，我们证明 JAM-A 通过抑制 Akt 依赖性β-连环蛋白激活，以二聚化依赖的方式限制肠上皮细胞（IEC）的增殖。此外，来自转基因 JAM-A(-/-)/β-连环蛋白/T 细胞因子报告小鼠的 IEC 显示出增强的β-连环蛋白依赖性转录。最后，Akt 的抑制作用逆转了 JAM-A 缺陷型小鼠结肠隐窝的过度增殖。这些数据在 JAM-A 和 IEC 稳态之间建立了新的联系。
