角质形成细胞介导的黑素细胞恶性逆转是一个由E-钙黏蛋白介导的过程，该过程优先于β-连环蛋白信号传导。

Reversal of melanocytic malignancy by keratinocytes is an E-cadherin-mediated process overriding beta-catenin signaling.

作者信息

Li Gang, Fukunaga Mizuho, Herlyn Meenhard

机构信息

The Wistar Institute, Philadelphia, PA 19104, USA.

出版信息

Exp Cell Res. 2004 Jul 1;297(1):142-51. doi: 10.1016/j.yexcr.2004.03.012.

DOI:10.1016/j.yexcr.2004.03.012

PMID:15194432

Abstract

Loss of E-cadherin in melanoma cells frees them from keratinocytes-mediated proliferation and phenotypic control, which can be restored by forced E-cadherin expression. In this study, E-cadherin and its derivatives were introduced into metastatic melanoma line 1205Lu. E-cadherin and E-cadherin-alpha-catenin fusion protein were functional in mediating cell adhesion, downregulating MCAM(4) in coculture, and inhibiting proliferation regardless of beta-catenin expression levels and activation status. In contrast, cytoplasmic domain-deleted (E-cadDeltaCYT) derivative was not able to reverse malignancy. The results indicate that E-cadherin-mediated cell adhesion is required for keratinocyte-mediated control of melanocytic cells, which can override proliferative activity of beta-catenin.

摘要

黑色素瘤细胞中E-钙黏蛋白的缺失使其摆脱了角质形成细胞介导的增殖和表型控制，而通过强制表达E-钙黏蛋白可恢复这种控制。在本研究中，将E-钙黏蛋白及其衍生物导入转移性黑色素瘤细胞系1205Lu。E-钙黏蛋白和E-钙黏蛋白-α-连环蛋白融合蛋白在介导细胞黏附、下调共培养中的MCAM(4)以及抑制增殖方面发挥作用，而与β-连环蛋白的表达水平和激活状态无关。相比之下，缺失细胞质结构域的(E-cadDeltaCYT)衍生物无法逆转恶性表型。结果表明，E-钙黏蛋白介导的细胞黏附是角质形成细胞介导的黑素细胞控制所必需的，这可以超越β-连环蛋白的增殖活性。