Collagen regulation of let-7 in pancreatic cancer involves TGF-β1-mediated membrane type 1-matrix metalloproteinase expression.
Collagen regulation of let-7 in pancreatic cancer involves TGF-β1-mediated membrane type 1-matrix metalloproteinase expression.
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DOI：
10.1038/onc.2010.485
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发表时间：
2011-02-24
期刊：
影响因子：
8
通讯作者：
Munshi, H. G.
中科院分区：
文献类型：
--
作者：
Dangi-Garimella, S.;Strouch, M. J.;Grippo, P. J.;Bentrem, D. J.;Munshi, H. G.
Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich fibrosis known as desmoplastic reaction; however the role of fibrosis in PDAC is poorly understood. In this report we show that collagen can regulate the tumor suppressive let-7 family of microRNAs in pancreatic cancer cells. PDAC cells growing in 3D collagen gels repress mature let-7 without affecting the precursor form of let-7 in part via increased expression of membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) and ERK1/2 activation. PDAC cells in collagen also demonstrate increased TGF-β1 signaling, and blocking TGF-β1 signaling attenuated collagen-induced MT1-MMP expression, ERK1/2 activation, and repression of let-7 levels. Although MT1-MMP overexpression was not sufficient to inhibit let-7 on 2D tissue culture plastic, overexpression of MT1-MMP in PDAC cells embedded in 3D collagen gels or grown in vivo repressed let-7 levels. Importantly, MT1-MMP expression significantly correlated with decreased levels of let-7 in human PDAC tumor specimens. Overall, our study emphasizes the interplay between the key proteinase MT1-MMP and its substrate type I collagen in modulating microRNA expression, and identifies an additional mechanism by which fibrosis may contribute to PDAC progression.
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影响因子：
4.8
作者：
Dangi-Garimella, Surabhi;Redig, Amanda J.;Munshi, Hidayatullah G.
通讯作者：
Munshi, Hidayatullah G.
影响因子：
64.5
作者：
Hotary, KB;Allen, ED;Weiss, SJ
通讯作者：
Weiss, SJ
DOI：
10.1073/pnas.0703942104
发表时间：
2007-10-09
影响因子：
11.1
作者：
Gironella, Meritxell;Seux, Mylene;Dusetti, Nelson J.
通讯作者：
Dusetti, Nelson J.
影响因子：
64.8
作者：
Reinhart, BJ;Slack, FJ;Ruvkun, G
通讯作者：
Ruvkun, G
影响因子：
29.4
作者：
Erkan, Mert;Kleeff, Joerg;Friess, Helmut
通讯作者：
Friess, Helmut