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bioRxiv · 10.1101/854562

Loss Of Nuclear Deformability Of Breast Cancer Cells By The Disruption Of Actin Filaments

Antmen, E.·Demirci, U.·Hasirci, V.
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Abstract

It is well known that chemical and biomechanical interactions between the nucleus and cytoskeleton are involved in and critical for movement, migration and nuclear positioning of cancer cells. Through nucleo-cytoskeletal coupling, proteins of the LINC complex and the nuclear envelope are capable of transducing cytoplasmic mechanical input across the nuclear membrane; however, their functional importance in the behavior of cancer cells and their nuclei has never been directly tested. In this study, our assumption was that the differences in the malignancies of breast cancer cells are the result of the differences in their nuclear deformation and its expression can be amplified on micropatterned surfaces. Based on this, our hypothesis was that the level of completeness of polymerization of actin filaments can affect nuclear deformability, and as a result, the metastatic capability of the cancer cells. In order to prove this we disrupted the polymerization of the actin filaments by using two drugs, Cytochalasin D and Jasplakinolide, which caused impaired propagation of intracellular forces, prevented nuclear deformation and increased in the expression levels of Lamin A/C and Nesprin-2 in malignant breast cancer cells. Our findings suggest that activity of these two proteins is critical for nucleo-cytoskeletal force transmission. More importantly, actin filament disruption can prevent the distortions in nuclear morphology and as a result avoid the development of cancer metastasis.

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Antmen, E., Demirci, U., Hasirci, V.. 2019-11-26. Loss Of Nuclear Deformability Of Breast Cancer Cells By The Disruption Of Actin Filaments. https://doi.org/10.1101/854562

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