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J Cell Biol. 2015 Feb 2;208(3):331-50. doi: 10.1083/jcb.201405099.

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

Author information

1
Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research; Proteomics Core Facility, National Heart, Lung, and Blood Institute; Biomolecular Engineering and Physical Sciences Shared Resource Program, National Institute of Biomolecular Imaging and Bioengineering; Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research; National Institutes of Health, Bethesda, MD 20892 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical School; and Department of Biostatistics, Bioinformatics, and Biomathematics; Georgetown University, Washington, DC 20057 vartym@mail.nih.gov kyamada@dir.nidcr.nih.gov.
2
Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research; Proteomics Core Facility, National Heart, Lung, and Blood Institute; Biomolecular Engineering and Physical Sciences Shared Resource Program, National Institute of Biomolecular Imaging and Bioengineering; Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research; National Institutes of Health, Bethesda, MD 20892.
3
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical School; and Department of Biostatistics, Bioinformatics, and Biomathematics; Georgetown University, Washington, DC 20057.
4
Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research; Proteomics Core Facility, National Heart, Lung, and Blood Institute; Biomolecular Engineering and Physical Sciences Shared Resource Program, National Institute of Biomolecular Imaging and Bioengineering; Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research; National Institutes of Health, Bethesda, MD 20892 vartym@mail.nih.gov kyamada@dir.nidcr.nih.gov.

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.

PMID:
25646088
PMCID:
PMC4315243
DOI:
10.1083/jcb.201405099
[Indexed for MEDLINE]
Free PMC Article

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