Department of Biosciences & Bioengineering, IIT Bombay, Mumbai, 400 076, India.
Sci Rep. 2017 Oct 27;7(1):14219. doi: 10.1038/s41598-017-14340-w.
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.
癌症通过致密的细胞外基质（ECM）的侵袭是由基质金属蛋白酶（MMPs）介导的，这些酶降解 ECM，从而为迁移创造了途径。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，我们通过研究 MMP 在调节与侵袭相关的癌细胞生物物理特性中的功能来解决这个问题。我们发现，MMP 的催化活性通过在膜上稳定整合素并激活粘着斑激酶来调节细胞的铺展、运动性、收缩性和皮质硬度。有趣的是，在 MMP 预处理表面上，抑制 MMP 诱导的细胞变圆和细胞在硬凝胶上变软的现象减弱了。总之，我们的结果表明，MMP 的催化活性通过调节整合素来调节癌细胞的侵袭性。
