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Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network.


ABSTRACT: 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.

SUBMITTER: Artym VV 

PROVIDER: S-EPMC4315243 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network.

Artym Vira V VV   Swatkoski Stephen S   Matsumoto Kazue K   Campbell Catherine B CB   Petrie Ryan J RJ   Dimitriadis Emilios K EK   Li Xin X   Mueller Susette C SC   Bugge Thomas H TH   Gucek Marjan M   Yamada Kenneth M KM  

The Journal of cell biology 20150201 3


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 f  ...[more]

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