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bioRxiv · 10.1101/598052

EMT-induced cell mechanical changes enhance mitotic rounding strength

Hosseini, K.·Taubenberger, A.·Werner, C.·Fischer-Friedrich, E.
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Abstract

To undergo mitosis successfully, most animal cells need to acquire a round shape to provide space for the mitotic spindle. This mitotic rounding relies on mechanical deformation of surrounding tissue and is driven by forces emanating from actomyosin contractility. Cancer cells are able to maintain successful mitosis in mechanically challenging environments such as the increasingly crowded environment of a growing tumor, thus, suggesting an enhanced ability of mitotic rounding in cancer. Here, we show that epithelial mesenchymal transition (EMT), a hallmark of cancer progression and metastasis, gives rise to cell-mechanical changes in breast epithelial cells. These changes are opposite in interphase and mitosis and correspond to an enhanced mitotic rounding strength. Furthermore, we show that cell-mechanical changes correlate with a strong EMT-induced change in the activity of Rho GTPases RhoA and Rac1. Accordingly, we find that Rac1 inhibition rescues the EMT-induced cortex-mechanical phenotype. Our findings hint at a new role of EMT in successful mitotic rounding and division in mechanically confined environments such as a growing tumor.

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Hosseini, K., Taubenberger, A., Werner, C., Fischer-Friedrich, E.. 2019-04-05. EMT-induced cell mechanical changes enhance mitotic rounding strength. https://doi.org/10.1101/598052

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