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Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network
Journal article   Open access   Peer reviewed

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

Vira V Artym, Stephen Swatkoski, Kazue Matsumoto, Catherine B Campbell, Ryan J Petrie, Emilios K Dimitriadis, Xin Li, Susette C Mueller, Thomas H Bugge, Marjan Gucek, …
The Journal of cell biology, v 208(3), pp 331-350
02 Feb 2015
PMID: 25646088
url
https://rupress.org/jcb/article-pdf/208/3/331/1366164/jcb_201405099.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1083/jcb.201405099View
Published, Version of Record (VoR) Open

Abstract

Animals Cell Line, Tumor Cell Surface Extensions - physiology Chickens Fibrillar Collagens - physiology Humans Integrin alpha2beta1 - metabolism Membrane Proteins - metabolism Neoplasm Proteins - metabolism Neoplasms - metabolism Neoplasms - pathology Phosphorylation Protein Processing, Post-Translational Signal Transduction
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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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
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