δ-Catenin promotes E-cadherin processing and activates β-catenin-mediated signaling: implications on human prostate cancer progression.
δ-Catenin promotes E-cadherin processing and activates β-catenin-mediated signaling: implications on human prostate cancer progression.
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DOI：
10.1016/j.bbadis.2011.12.015
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发表时间：
2012-04
影响因子：
6.2
通讯作者：
Kim, Kwonseop
中科院分区：
文献类型：
--
作者：
Kim, Hangun;He, Yongfeng;Yang, Ilhwan;Zeng, Yan;Kim, Yonghee;Seo, Young-Woo;Murnane, Mary Jo;Jung, Chaeyong;Lee, Jae-Hyuk;Min, Jeong-Joon;Kwon, Dong-Deuk;Kim, Kyung Keun;Lu, Qun;Kim, Kwonseop
δ-Catenin结合E-cadherin的近膜结构域，已知在一些人类肿瘤中过表达。然而，δ-catenin在上皮细胞和癌中的功能尚不清楚。我们发现过表达δ-catenin的前列腺癌细胞在培养中表现出多层生长的增加。在这些细胞中，δ-catenin与E-cadherin在质膜上共定位，E-cadherin加工明显升高。δ-catenin诱导的E-Cadherin加工是血清依赖性的，需要MMP-和PS-1/γ-分泌酶介导的活性。δ-catenin的缺失突变体剥夺了δ-catenin结合E-cadherin或将PS-1招募到E-cadherin的能力，完全消除了δ-catenin诱导的E-cadherin加工和细胞的多层生长。此外，过表达δ-catenin的前列腺癌细胞显示总β-catenin水平升高，细胞核分布增加，导致β-catenin/ lef -1介导的转录及其下游靶基因以及雄激素受体介导的转录被激活。确实，来源于过表达δ-catenin细胞的裸鼠人前列腺肿瘤异种移植物显示出β-catenin核定位增加，生长速度更快。此外，转移性异种移植物肿瘤的重量与29 kD E-cadherin片段的水平呈正相关，原发人前列腺肿瘤组织中δ-catenin的表达和E-cadherin加工水平也有所升高。综上所述，这些结果表明δ-catenin通过诱导E-cadherin加工，从而激活β-catenin介导的致癌信号，在前列腺癌的进展中发挥重要作用。
δ-Catenin binds the juxtamembrane domain of E-cadherin and is known to be overexpressed in some human tumors. However, the functions of δ-catenin in epithelial cells and carcinomas remain elusive. We found that prostate cancer cells overexpressing δ-catenin show an increase in multi-layer growth in culture. In these cells, δ-catenin colocalizes with E-cadherin at the plasma membrane, and the E-cadherin processing is noticeably elevated. E-Cadherin processing induced by δ-catenin is serum-dependent and requires MMP- and PS-1/γ-secretase-mediated activities. A deletion mutant of δ-catenin that deprives the ability of δ-catenin to bind E-cadherin or to recruit PS-1 to E-cadherin totally abolishes the δ-catenin-induced E-cadherin processing and the multilayer growth of the cells. In addition, prostate cancer cells overexpressing δ-catenin display an elevated total β-catenin level and increase nuclear distribution, resulting in the activation of β-catenin/LEF-1-mediated transcription and their downstream target genes as well as androgen receptor-mediated transcription. Indeed, human prostate tumor xenograft in nude mice, which is derived from cells overexpressing δ-catenin, shows increased β-catenin nuclear localization and more rapid growth rates. Moreover, the metastatic xenograft tumor weights positively correlate with the level of 29 kD E-cadherin fragment, and primary human prostate tumor tissues also show elevated levels of δ-catenin expression and the E-cadherin processing. Taken together, these results suggest that δ-catenin plays an important role in prostate cancer progression through inducing E-cadherin processing and thereby activating β-catenin-mediated oncogenic signals.
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影响因子：
64.5
作者：
Drees, F;Pokutta, S;Weis, WI
通讯作者：
Weis, WI
影响因子：
4.8
作者：
Kouchi, Zen;Barthet, Gael;Robakis, Nikolaos K.
通讯作者：
Robakis, Nikolaos K.
影响因子：
3.3
作者：
Kiss, Alexi;Troyanovsky, Regina B.;Troyanovsky, Sergey M.
通讯作者：
Troyanovsky, Sergey M.
影响因子：
3.9
作者：
Ki, Hyunkyoung;Oh, Minsoo;Kim, Kwonseop
通讯作者：
Kim, Kwonseop
DOI：
10.1016/j.bbrc.2008.02.069
发表时间：
2008-05-02
影响因子：
3.1
作者：
Kim, Kwonseop;Oh, Minsoo;Lu, Qun
通讯作者：
Lu, Qun