Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network.
Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network.
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DOI：
10.1083/jcb.201405099
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发表时间：
2015-02-02
期刊：
影响因子：
--
通讯作者：
Yamada KM
中科院分区：
文献类型：
--
作者：
Artym VV;Swatkoski S;Matsumoto K;Campbell CB;Petrie RJ;Dimitriadis EK;Li X;Mueller SC;Bugge TH;Gucek M;Yamada KM
高密度纤维状胶原基质通过依赖Kindlin2的机制诱导成纤维细胞和癌细胞系形成内翻足，从而驱动局部ECM重塑。细胞与细胞外基质(ECM)的相互作用可以在动态的双向过程中调节多种细胞活动和基质本身。其中一个过程是ECM的局部蛋白水解性修饰。肿瘤细胞的侵袭性是富含肌动蛋白的蛋白水解性突起，可局部降解基质分子并介导侵袭。我们报道了一种新的高密度纤维状胶原(HDFC)基质是一种有效的诱导剂，在癌细胞系和原代人成纤维细胞中都是如此。在癌细胞中，HDFC基质通过一种不需要生长因子甚至不改变基因和蛋白质表达的特定整合素信号通路诱导形成不动足。相比之下，磷酸蛋白质组学发现了一个复杂的磷酸信号网络中的重大变化，Kindlin2丝氨酸磷酸化是一个关键的调节元件。这种依赖Kindlin2的信号转导网络是有效地诱导致密纤维胶原上的内陷和胶原的局部降解所必需的。这种新的磷信号机制通过kindlin2调节细胞表面的内陷，从而实现细胞外基质的局部蛋白水解性重塑。
High-density fibrillar collagen matrix induces invadopodia formation in both fibroblasts and carcinoma cell lines through a kindlin2-dependent mechanism that drives local ECM remodeling. Cell interactions with the extracellular matrix (ECM) can regulate multiple cellular activities and the matrix itself in dynamic, bidirectional processes. One such process is local proteolytic modification of the ECM. Invadopodia of tumor cells are actin-rich proteolytic protrusions that locally degrade matrix molecules and mediate invasion. We report that a novel high-density fibrillar collagen (HDFC) matrix is a potent inducer of invadopodia, both in carcinoma cell lines and in primary human fibroblasts. In carcinoma cells, HDFC matrix induced formation of invadopodia via a specific integrin signaling pathway that did not require growth factors or even altered gene and protein expression. In contrast, phosphoproteomics identified major changes in a complex phosphosignaling network with kindlin2 serine phosphorylation as a key regulatory element. This kindlin2-dependent signal transduction network was required for efficient induction of invadopodia on dense fibrillar collagen and for local degradation of collagen. This novel phosphosignaling mechanism regulates cell surface invadopodia via kindlin2 for local proteolytic remodeling of the ECM.
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DOI：
10.1111/j.1742-4658.2009.06893.x
发表时间：
2009-03
期刊：
The FEBS journal
影响因子：
--
作者：
Debrand E;El Jai Y;Spence L;Bate N;Praekelt U;Pritchard CA;Monkley SJ;Critchley DR
通讯作者：
Critchley DR
影响因子：
9.2
作者：
Bravo-Cordero, Jose Javier;Oser, Matthew;Chen, Xiaoming;Eddy, Robert;Hodgson, Louis;Condeelis, John
通讯作者：
Condeelis, John
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
3.3
作者：
Beaty BT;Sharma VP;Bravo-Cordero JJ;Simpson MA;Eddy RJ;Koleske AJ;Condeelis J
通讯作者：
Condeelis J
影响因子：
6.4
作者：
ENGVALL, E;RUOSLAHTI, E
通讯作者：
RUOSLAHTI, E