p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression.
p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression.
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DOI：
10.1083/jcb.200805113
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发表时间：
2008-11-17
期刊：
影响因子：
--
通讯作者：
Anastasiadis PZ
中科院分区：
文献类型：
--
作者：
Soto E;Yanagisawa M;Marlow LA;Copland JA;Perez EA;Anastasiadis PZ
P120连环蛋白以黏附依赖的方式调节Rho家族鸟苷三磷酸酶(包括RhoA和rac1)的活性。通过这一作用，p120在与上皮钙粘附素(E-cadherin)相关时促进固位型细胞表型，在与间充质钙粘附素相关时促进运动型细胞表型。在这项研究中，我们发现p120对肿瘤细胞的生长也有显著的和截然相反的作用，这依赖于E-钙粘附素的表达。内源性p120起稳定E-钙粘素复合体的作用，并积极促进E-钙粘附素的抑瘤功能，有效抑制RAS的激活。当肿瘤进展过程中E-钙粘蛋白丢失时，RAS的负调控被解除；在这些条件下，内源性p120通过激活通常由细胞与细胞外基质黏附激活的rac1丝裂原激活的蛋白激酶信号通路来促进转化细胞在体外和体内的生长。这些数据表明，E-钙粘蛋白和p120都是肿瘤细胞生长的重要调节因子，并暗示了这两种蛋白在化疗耐药和靶向治疗中的作用。
p120 catenin regulates the activity of the Rho family guanosine triphosphatases (including RhoA and Rac1) in an adhesion-dependent manner. Through this action, p120 promotes a sessile cellular phenotype when associated with epithelial cadherin (E-cadherin) or a motile phenotype when associated with mesenchymal cadherins. In this study, we show that p120 also exerts significant and diametrically opposing effects on tumor cell growth depending on E-cadherin expression. Endogenous p120 acts to stabilize E-cadherin complexes and to actively promote the tumor-suppressive function of E-cadherin, potently inhibiting Ras activation. Upon E-cadherin loss during tumor progression, the negative regulation of Ras is relieved; under these conditions, endogenous p120 promotes transformed cell growth both in vitro and in vivo by activating a Rac1–mitogen-activated protein kinase signaling pathway normally activated by the adhesion of cells to the extracellular matrix. These data indicate that both E-cadherin and p120 are important regulators of tumor cell growth and imply roles for both proteins in chemoresistance and targeted therapeutics.
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DOI：
10.1083/jcb.153.5.1049
发表时间：
2001-05-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gottardi CJ;Wong E;Gumbiner BM
通讯作者：
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影响因子：
2.6
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DOI：
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发表时间：
1989-06
期刊：
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影响因子：
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