MMP proteolytic activity regulates cancer invasiveness by modulating integrins.
MMP proteolytic activity regulates cancer invasiveness by modulating integrins.
复制标题
DOI：
10.1038/s41598-017-14340-w
复制
发表时间：
2017-10-27
影响因子：
4.6
通讯作者：
Sen S
中科院分区：
文献类型：
--
作者：
Das A;Monteiro M;Barai A;Kumar S;Sen S
通过致密细胞外基质（ECM）的癌症侵袭由基质金属蛋白酶（MMP）介导，所述基质金属蛋白酶降解ECM，从而产生迁移路径。然而，这种降解如何影响癌细胞的表型尚不完全清楚。在这里，我们解决这个问题，通过探测MMPs的功能，在调节生物物理特性的癌细胞相关的入侵。我们发现MMP催化活性通过稳定膜上的整合素和激活粘着斑激酶来调节细胞的伸展、运动性、收缩性和皮质硬度。有趣的是，MMP抑制诱导的硬凝胶上的细胞变圆和细胞软化在MMP预处理的表面上减弱。总之，我们的研究结果表明，MMP催化活性调节癌细胞的侵袭性，通过调节整合素。
Cancer invasion through dense extracellular matrices (ECMs) is mediated by matrix metalloproteinases (MMPs) which degrade the ECM thereby creating paths for migration. However, how this degradation influences the phenotype of cancer cells is not fully clear. Here we address this question by probing the function of MMPs in regulating biophysical properties of cancer cells relevant to invasion. We show that MMP catalytic activity regulates cell spreading, motility, contractility and cortical stiffness by stabilizing integrins at the membrane and activating focal adhesion kinase. Interestingly, cell rounding and cell softening on stiff gels induced by MMP inhibition is attenuated on MMP pre-conditioned surfaces. Together, our results suggest that MMP catalytic activity regulates invasiveness of cancer cells by modulating integrins.
登录
查看更多内容
影响因子：
2.8
作者：
Davidson, Patricia M.;Denais, Celine;Bakshi, Maya C.;Lammerding, Jan
通讯作者：
Lammerding, Jan
影响因子：
4
作者：
Humphries JD;Byron A;Humphries MJ
通讯作者：
Humphries MJ
影响因子：
11.4
作者：
Gutierrez-Fernandez, Ana;Soria-Valles, Clara;Lopez-Otin, Carlos
通讯作者：
Lopez-Otin, Carlos
影响因子：
3.4
作者：
Lee, Meng-Horng;Wu, Pei-Hsun;Wirtz, Denis
通讯作者：
Wirtz, Denis
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA