Regulation of MT1-MMP activity by β-catenin in MDCK non-cancer and HT1080 cancer cells.
Regulation of MT1-MMP activity by β-catenin in MDCK non-cancer and HT1080 cancer cells.
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DOI：
10.1002/jcp.22292
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发表时间：
2010-11
影响因子：
5.6
通讯作者：
Wilson, Michael J.
中科院分区：
文献类型：
--
作者：
Liu, Ping;Yang, Jianbo;Pei, Jing;Pei, Duanqing;Wilson, Michael J.
过去对β-catenin在癌细胞中的研究集中在核定位的β-catenin及其参与Wnt通路。本研究旨在探讨β-catenin在细胞质和细胞核中对MT1-MMP表达和活性的调节作用。我们发现MDCK非癌细胞中的β-连环蛋白通过与胞质中MT1-MMP的18个氨基酸胞质尾直接相互作用来抑制MT1-MMP的细胞表面定位，从而抑制其对pro-MMP 2活化的蛋白水解活性。而HT 1080细胞中的β-catenin则通过进入细胞核激活转录因子Tcf-4/Lef，提高MT1-MMP蛋白水平，从而增强MT1-MMP的活性。我们还发现，在3-D/2-D I型胶原凝胶中的细胞生长和MT1-MMP对细胞迁移的促进作用在MDCK细胞中被β-catenin抑制，而在HT 1080细胞中这些功能被增强。此外，β-catenin对MT1-MMP的调控还涉及MDCK细胞中的E-cadherin和HT 1080细胞中的Wnt-3a。综上所述，我们的研究结果表明，在非癌细胞和癌细胞中，胞质和核β-连环蛋白对MT1-MMP活性的影响不同。这些差异很可能是由于β-catenin在这些细胞中的不同亚细胞位置和不同的参与途径。
Past studies on β-catenin in cancer cells focused on nuclear localized β-catenin and its involvement in the Wnt pathway. Our goal here was to investigate the function of β-catenin in both the cytoplasm and nucleus on the regulation of MT1-MMP expression and activity. We found that β-catenin in MDCK non-cancer cells inhibited the cell surface localization of MT1-MMP, and thus its proteolytic activity on pro-MMP2 activation, via direct interaction with the 18-amino acid cytoplasmic tail of MT1-MMP in the cytoplasm. In contrast, β-catenin in HT1080 cancer cells enhanced the activity of MT1-MMP by entering the nucleus and activating transcription factor Tcf-4/Lef, and elevating the level of MT1-MMP protein. We also found that enhancement of cell growth in 3-D/2-D type I collagen gels and of cell migration by MT1-MMP were inhibited by β-catenin in MDCK cells, whereas these functions were enhanced in HT1080 cells. In addition, regulation of MT1-MMP by β-catenin involved E-cadherin in MDCK cells and Wnt-3a in HT1080 cells. Taken together, our results present a differential effect of cytoplasmic and nuclear β-catenin on MT1-MMP activity in non-cancer cells versus cancer cells. These differences were most probably due to different subcellular locations and different involved pathways of β-catenin in these cells.
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影响因子：
11.2
作者：
Li, YY;Aoki, T;Sato, H
通讯作者：
Sato, H
影响因子：
11.4
作者：
Bravo-Cordero, Jose J.;Marrero-Diaz, Raquel;Montoya, Maria C.
通讯作者：
Montoya, Maria C.
影响因子：
64.5
作者：
Hiraoka, N;Allen, E;Weiss, SJ
通讯作者：
Weiss, SJ
DOI：
10.1152/ajprenal.00179.2005
发表时间：
2006-01-01
影响因子：
4.2
作者：
Covington, MD;Burghardt, RC;Parrish, AR
通讯作者：
Parrish, AR
影响因子：
11.4
作者：
Itoh, Y;Takamura, A;Seiki, M
通讯作者：
Seiki, M