LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration.
LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration.
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DOI：
10.1038/s41467-018-04865-7
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发表时间：
2018-06-22
影响因子：
16.6
通讯作者：
Chavrier P
中科院分区：
文献类型：
--
作者：
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
癌细胞通过组织基质中收缩孔迁移的能力受到核硬度的限制。MT 1-MMP通过扩大基质孔隙，促进受限的迁移而促进转移。在这里，我们表明，已知调节核硬度的基质孔径或层粘连蛋白A表达的调节直接影响癌细胞MT 1-MMP介导的细胞周胶原溶解的水平。这种适应性反应的一个组成部分是MT 1-MMP细胞内储存隔室在细胞核前面的中心体为中心的分布。我们进一步表明，这种反应，包括invadopodia的形成与限制基质纤维，需要通过核骨架和细胞骨架（LINC）复合蛋白nesprin-2和动力蛋白适配器Lis 1的接头的核和中心体之间的完整连接。我们的研究结果揭示了一种按需策略，通过狭窄的空间进行核转位，从而限制迁移触发了MT 1-MMP储存室的极化和细胞核前的基质蛋白水解，这取决于细胞核-微管连接。癌细胞通过小的狭窄区域迁移的能力受到核硬度的限制。在这里，作者表明，反过来，核硬度刺激酶的传递，这些酶对细胞外基质的降解和与纤维相关的侵入伪足的形成很重要，从而对抗核运动。
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. The ability of cancer cells to migrate through small, constricted areas is limited by nuclear stiffness. Here the authors show that in turn nuclear stiffness stimulates the delivery of enzymes important for the degradation of the extracellular matrix and the formation of invadopodia in association with fibers thus opposing nuclear movement.
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影响因子：
2.8
作者：
Davidson, Patricia M.;Denais, Celine;Bakshi, Maya C.;Lammerding, Jan
通讯作者：
Lammerding, Jan
LIS1和NDEL1会影响神经干细胞中核膜分解的时机。
影响因子：
7.8
作者：
Hebbar, Sachin;Mesngon, Mariano T.;Guillotte, Aimee M.;Desai, Bhavim;Ayala, Ramses;Smith, Deanna S.
通讯作者：
Smith, Deanna S.
影响因子：
3.3
作者：
Irianto J;Pfeifer CR;Bennett RR;Xia Y;Ivanovska IL;Liu AJ;Greenberg RA;Discher DE
通讯作者：
Discher DE
DOI：
10.1083/jcb.201004118
发表时间：
2010-10-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fridolfsson HN;Starr DA
通讯作者：
Starr DA
影响因子：
2.8
作者：
Irianto J;Pfeifer CR;Ivanovska IL;Swift J;Discher DE
通讯作者：
Discher DE