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Mechanobiology of Disease
Poster Abstracts
105
18-POS
Board 18
Nuclear and Cellular Softening is Essential for Invasive Cancer Cells to Migrate and
Metastasize
Alakesh Das
, Sandeep Kumar, Shamik Sen.
IIT Bombay, Mumbai, Maharashtra, India.
Cancer cells metastasis is a multistep complicated process in which cellular biophysical
modifications plays one of the very crucial role. During mesenchymal to amoeboidal transition
cancer cells undergo certain physical deformations which allows them to migrate through dense
3D matrices. However, it is still not clear how cells induce these modifications and what is the
molecular mechanism behind this transformations. Here in our work using highly invasive
MDA-MB-231 and HT-1080 cells and less invasive MCF-7 cells we have first demonstrated the
existence of an integrin-mediated bi-directional crosstak between MMPs and actomyosin
contractility. Further, we have shown that GM6001 treatment induces cellular and nuclear
softening. To probe the functional relevance of this biophysical alteration we performed
sandwich gel 3D invasion assay and observed that GM6001 treated cells were migration as
efficiently as untreated cells. However, addition of divalent cations reversed this softening
effects and cells were stuck in their migratory tracks. Further using computational approach we
provided the conclusion that both cellular and nuclear plasticity is essential for cells to undergo
migration through tight and narrow interfaces.