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LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration

Author

Listed:
  • Elvira Infante

    (PSL Research University)

  • Alessia Castagnino

    (PSL Research University)

  • Robin Ferrari

    (PSL Research University)

  • Pedro Monteiro

    (PSL Research University)

  • Sonia Agüera-González

    (PSL Research University)

  • Perrine Paul-Gilloteaux

    (PSL Research University
    Cell and Tissue Imaging Facility (PICT-IBiSA))

  • Mélanie J. Domingues

    (PSL Research University)

  • Paolo Maiuri

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Matthew Raab

    (PSL Research University)

  • Catherine M. Shanahan

    (King’s College)

  • Alexandre Baffet

    (PSL Research University)

  • Matthieu Piel

    (PSL Research University)

  • Edgar R. Gomes

    (Universidade de Lisboa)

  • Philippe Chavrier

    (PSL Research University)

Abstract

Cancer cells’ ability to migrate through constricting pores in the tissue matrix is limited by nuclear stiffness. MT1-MMP contributes to metastasis by widening matrix pores, facilitating confined migration. Here, we show that modulation of matrix pore size or of lamin A expression known to modulate nuclear stiffness directly impinges on levels of MT1-MMP-mediated pericellular collagenolysis by cancer cells. A component of this adaptive response is the centrosome-centered distribution of MT1-MMP intracellular storage compartments ahead of the nucleus. We further show that this response, including invadopodia formation in association with confining matrix fibrils, requires an intact connection between the nucleus and the centrosome via the linker of nucleoskeleton and cytoskeleton (LINC) complex protein nesprin-2 and dynein adaptor Lis1. Our results uncover a digest-on-demand strategy for nuclear translocation through constricted spaces whereby confined migration triggers polarization of MT1-MMP storage compartments and matrix proteolysis in front of the nucleus depending on nucleus-microtubule linkage.

Suggested Citation

  • Elvira Infante & Alessia Castagnino & Robin Ferrari & Pedro Monteiro & Sonia Agüera-González & Perrine Paul-Gilloteaux & Mélanie J. Domingues & Paolo Maiuri & Matthew Raab & Catherine M. Shanahan & A, 2018. "LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04865-7
    DOI: 10.1038/s41467-018-04865-7
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    Cited by:

    1. Apeksha Shapeti & Jorge Barrasa-Fano & Abdel Rahman Abdel Fattah & Janne Jong & José Antonio Sanz-Herrera & Mylène Pezet & Said Assou & Emilie Vet & Seyed Ali Elahi & Adrian Ranga & Eva Faurobert & Ha, 2024. "Force-mediated recruitment and reprogramming of healthy endothelial cells drive vascular lesion growth," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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