Regulation of the stability of cell surface E-cadherin by the proteasome
Regulation of the stability of cell surface E-cadherin by the proteasome
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DOI：
10.1016/j.bbrc.2009.02.098
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发表时间：
2009-04-17
影响因子：
3.1
通讯作者：
Miyazono, Kohei
中科院分区：
文献类型：
--
作者：
Saitoh, Masao;Shirakihara, Takuya;Miyazono, Kohei
上皮间质转化 (EMT) 是癌症进展和胚胎发育中的一个关键事件，由转化生长因子 (TGF)-β 诱导。 E-钙粘蛋白（一种代表性上皮标志物）的表达。通过 TGF-β 的转录减少来抑制。在这里，我们发现，在正常上皮细胞和癌细胞中，在 TGF-β 诱导的 EMT 过程中和肝细胞生长因子 (HGF) 诱导的散射过程中，细胞表面 E-钙粘蛋白的内吞作用可以通过用乳胞素和 MG132 抑制蛋白酶体来阻断。尽管 TGF-β 处理后细胞表面 E-钙粘蛋白的丢失导致 P-连环蛋白（一种 E-钙粘蛋白锚定分子）易位至细胞核，但蛋白酶体抑制阻止了这一过程，并导致 β-连环蛋白与 E-钙粘蛋白在细胞表面共定位，导致细胞与细胞粘附的建立。然而，TGF-β促进细胞迁移并没有受到蛋白酶体抑制的显着影响。因此，蛋白酶体依赖性事件似乎与细胞表面 E-钙粘蛋白的稳定有关。 (C) 2009 Elsevier Inc. 保留所有权利。
The epithelial-mesenchymal transition (EMT), a crucial event in cancer progression and embryonic development, is induced by transforming growth factor (TGF)-beta. Expression of E-cadherin, a representative epithelial marker. is repressed through transcriptional reduction by TGF-beta. Here, we show that endocytosis of cell surface E-cadherin during EMT induced by TGF-beta and during scattering induced by hepatocyte growth factor (HGF) can be blocked by inhibiting proteasome with lactacystin and MG132 in normal epithelial cells and in cancer cells. Although loss of cell surface E-cadherin following TGF-beta treatment induced translocation of P-catenin, an E-cadherin-anchoring molecule, to the nucleus, proteasome inhibition prevented this process and resulted in co-localization of beta-catenin with E-cadherin at the cell surface, leading to establishment of cell-cell adhesion. However, promotion of cell migration by TGF-beta was not significantly affected by proteasome inhibition. Proteasome-dependent events thus appear to be involved in stabilization of cell surface E-cadherin. (C) 2009 Elsevier Inc. All rights reserved.