Cancer Cells Resist Mechanical Destruction in Circulation via RhoA/Actomyosin-Dependent Mechano-Adaptation
| Autor: | Benjamin L Krog, Christopher S. Stipp, Sophia Williams-Perez, Patrick Breheny, Lei Zhao, Mohammed M. Milhem, Devon L. Moose, Gretchen Burke, Amy C. Rowat, Lillian Rhodes, Marion Vanneste, Michael D. Henry, Tae-Young Kim |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
RHOA fluid shear stress Cell Survival formin Medical Physiology Adaptation Biological circulating tumor cells General Biochemistry Genetics and Molecular Biology Article Metastasis 03 medical and health sciences 0302 clinical medicine Circulating tumor cell myosin II Cell Line Tumor Neoplasms Myosin medicine metastasis Animals Humans Neoplasm Metastasis lcsh:QH301-705.5 Hemodynamic forces Myosin Type II biology Chemistry Cell Membrane Hemodynamics Fluid shear stress RhoA Actomyosin medicine.disease Neoplastic Cells Circulating Cell biology Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) Formins Cancer cell biology.protein Biochemistry and Cell Biology Stress Mechanical Shear Strength rhoA GTP-Binding Protein 030217 neurology & neurosurgery |
| Zdroj: | Cell Rep Cell Reports, Vol 30, Iss 11, Pp 3864-3874.e6 (2020) Cell reports, vol 30, iss 11 |
| ISSN: | 2211-1247 |
| Popis: | Summary: During metastasis, cancer cells are exposed to potentially destructive hemodynamic forces including fluid shear stress (FSS) while en route to distant sites. However, prior work indicates that cancer cells are more resistant to brief pulses of high-level FSS in vitro relative to non-transformed epithelial cells. Herein, we identify a mechano-adaptive mechanism of FSS resistance in cancer cells. Our findings demonstrate that cancer cells activate RhoA in response to FSS, which protects them from FSS-induced plasma membrane damage. We show that cancer cells freshly isolated from mouse and human tumors are resistant to FSS, that formin and myosin II activity protects circulating tumor cells (CTCs) from destruction, and that short-term inhibition of myosin II delays metastasis in mouse models. Collectively, our data indicate that viable CTCs actively resist destruction by hemodynamic forces and are likely to be more mechanically robust than is commonly thought. : Moose et al. show that cancer cells exhibit a mechano-adaptive response to fluid shear stress through activation of the RhoA-actomyosin signaling axis. Utilizing in vivo models, they extend these findings to demonstrate that this axis maintains intravascular survival of circulating tumor cells (CTCs) that contributes to the development of metastasis. Keywords: fluid shear stress, circulating tumor cells, metastasis, RhoA, myosin II, formin |
| Databáze: | OpenAIRE |
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