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

Elvira Infante; Alessia Castagnino; Robin Ferrari; Pedro Monteiro; Sonia Agüera-gonzález; Perrine Paul-gilloteaux; Mélanie J. Domingues; Paolo Maiuri; Matthew Raab; Catherine M. Shanahan; Alexandre Baffet; Matthieu Piel; Edgar R. Gomes; Philippe Chavrier

doi:10.1038/s41467-018-04865-7

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

Elvira Infante, Alessia Castagnino, Robin Ferrari, Pedro Monteiro, Sonia Agüera-gonzález, Perrine Paul-gilloteaux, Mélanie J. Domingues, Paolo Maiuri, Matthew Raab, Catherine M. Shanahan, Alexandre Baffet, Matthieu Piel, Edgar R. Gomes, Philippe Chavrier

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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.

Original language	English
Journal	Nature Communications
Volume	9
Issue number	1
Early online date	22 Jun 2018
DOIs	https://doi.org/10.1038/s41467-018-04865-7
Publication status	Published - 1 Dec 2018

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Infante, E., Castagnino, A., Ferrari, R., Monteiro, P., Agüera-gonzález, S., Paul-gilloteaux, P., Domingues, M. J., Maiuri, P., Raab, M., Shanahan, C. M., Baffet, A., Piel, M., Gomes, E. R., & Chavrier, P. (2018). LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-04865-7

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

abstract = "Cancer cells{\textquoteright} 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.",

author = "Elvira Infante and Alessia Castagnino and Robin Ferrari and Pedro Monteiro and Sonia Ag{\"u}era-gonz{\'a}lez and Perrine Paul-gilloteaux and Domingues, {M{\'e}lanie J.} and Paolo Maiuri and Matthew Raab and Shanahan, {Catherine M.} and Alexandre Baffet and Matthieu Piel and Gomes, {Edgar R.} and Philippe Chavrier",

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Infante, E, Castagnino, A, Ferrari, R, Monteiro, P, Agüera-gonzález, S, Paul-gilloteaux, P, Domingues, MJ, Maiuri, P, Raab, M, Shanahan, CM, Baffet, A, Piel, M, Gomes, ER & Chavrier, P 2018, 'LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration', Nature Communications, vol. 9, no. 1. https://doi.org/10.1038/s41467-018-04865-7

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T1 - LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration

AU - Infante, Elvira

AU - Castagnino, Alessia

AU - Ferrari, Robin

AU - Monteiro, Pedro

AU - Agüera-gonzález, Sonia

AU - Paul-gilloteaux, Perrine

AU - Domingues, Mélanie J.

AU - Maiuri, Paolo

AU - Raab, Matthew

AU - Shanahan, Catherine M.

AU - Baffet, Alexandre

AU - Piel, Matthieu

AU - Gomes, Edgar R.

AU - Chavrier, Philippe

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-018-04865-7

M3 - Article

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

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