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http://hdl.handle.net/10397/94105
Title: | Fluid shear stress regulates the survival of circulating tumor cells via nuclear expansion | Authors: | Xu, Z Li, K Xin, Y Tan, K Yang, M Wang, G Tan, Y |
Issue Date: | May-2022 | Source: | Journal of cell science, May 2022, v. 135, no. 10, jcs259586 | Abstract: | Distant metastasis mainly occurs through hematogenous dissemination, where suspended circulating tumor cells (CTCs) experience a considerable level of fluid shear stress. We recently reported that shear flow induced substantial apoptosis of CTCs, although a small subpopulation could still persist. However, how suspended tumor cells survive in shear flow remains poorly understood. This study finds that fluid shear stress eliminates the majority of suspended CTCs and increases nuclear size, whereas it has no effect on the viability of adherent tumor cells and decreases their nuclear size. Shear flow promotes histone acetylation in suspended tumor cells, the inhibition of which using one drug suppresses shear-induced nuclear expansion, suggesting that shear stress might increase nuclear size through histone acetylation. Suppressing histone acetylation-mediated nuclear expansion enhances shear-induced apoptosis of CTCs. These findings suggest that suspended tumor cells respond to shear stress through histone acetylation-mediated nuclear expansion, which protects CTCs from shear-induced destruction. Our study elucidates a unique mechanism underlying the mechanotransduction of suspended CTCs to shear flow, which might hold therapeutic promise for CTC eradication. | Keywords: | Circulating tumor cell Fluid shear stress Histone acetylation Mechanobiology Nuclear size |
Publisher: | Company of Biologists | Journal: | Journal of cell science | ISSN: | 0021-9533 | EISSN: | 1477-9137 | DOI: | 10.1242/jcs.259586 | Rights: | © 2022. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. The following publication Xu, Z., Li, K., Xin, Y., Tan, K., Yang, M., Wang, G., & Tan, Y. (2022). Fluid shear stress regulates the survival of circulating tumor cells via nuclear expansion. Journal of Cell Science, 135(10), jcs259586 is available at https://doi.org/10.1242/jcs.259586. |
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