Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
Exp Cell Res. 2011 Apr 1;317(6):838-48. doi: 10.1016/j.yexcr.2010.12.025. Epub 2011 Jan 4.
High levels of the soluble form of E-cadherin can be found in the serum of cancer patients and are associated with poor prognosis. Despite the possible predictive value of soluble E-cadherin, little is understood concerning its patho-physiological consequences in tumor progression. In this study, we show that soluble E-cadherin facilitates cell survival via functional interaction with cellular E-cadherin. Exposure of cells to a recombinant form of soluble E-cadherin, at a concentration found in cancer patient's serum, prevents apoptosis due to serum/growth factor withdrawal, and inhibits epithelial lumen formation, a process that requires apoptosis. Further, soluble E-cadherin-mediated cell survival involves activation of the epidermal growth factor receptor (EGFR) and EGFR-mediated activation of both phosphoinositide-3 kinase (PI3K)/AKT and ERK1/2 signaling pathways. These results are evidence of a complex functional interplay between EGFR and E-cadherin and also suggest that the presence of soluble E-cadherin in cancer patients' sera might have relevance to cell survival and tumor progression.
高水平的可溶性 E-钙黏蛋白可在癌症患者的血清中被发现，并且与不良预后相关。尽管可溶性 E-钙黏蛋白可能具有预测价值，但对于其在肿瘤进展中的病理生理后果，人们知之甚少。在这项研究中，我们表明可溶性 E-钙黏蛋白通过与细胞内 E-钙黏蛋白的功能相互作用促进细胞存活。将细胞暴露于在癌症患者血清中发现的浓度的重组可溶性 E-钙黏蛋白形式中，可防止因血清/生长因子撤出而导致的细胞凋亡，并抑制需要凋亡的上皮腔形成过程。此外，可溶性 E-钙黏蛋白介导的细胞存活涉及表皮生长因子受体（EGFR）的激活以及 EGFR 介导的磷酸肌醇-3-激酶（PI3K）/AKT 和 ERK1/2 信号通路的激活。这些结果证明了 EGFR 和 E-钙黏蛋白之间的复杂功能相互作用，并且还表明癌症患者血清中存在可溶性 E-钙黏蛋白可能与细胞存活和肿瘤进展有关。
