Cancer Cells Resist Mechanical Destruction in Circulation via RhoA/Actomyosin-Dependent Mechano-Adaptation

Devon L Moose; Benjamin L Krog; Tae-Hyung Kim; Lei Zhao; Sophia Williams-Perez; Gretchen Burke; Lillian Rhodes; Marion Vanneste; Patrick Breheny; Mohammed Milhem; Christopher S Stipp; Amy C Rowat; Michael D Henry

doi:10.1016/j.celrep.2020.02.080

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Cancer Cells Resist Mechanical Destruction in Circulation via RhoA/Actomyosin-Dependent Mechano-Adaptation

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Cancer Cells Resist Mechanical Destruction in Circulation via RhoA/Actomyosin-Dependent Mechano-Adaptation

Devon L Moose, Benjamin L Krog, Tae-Hyung Kim, Lei Zhao, Sophia Williams-Perez, Gretchen Burke, Lillian Rhodes, Marion Vanneste, Patrick Breheny, Mohammed Milhem, …

Cell reports (Cambridge), Vol.30(11), pp.3864-3874.e6

03/17/2020

DOI: 10.1016/j.celrep.2020.02.080

PMCID: PMC7219793

PMID: 32187555

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Abstract

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. [Display omitted] •Cancer cells from primary tumors are resistant to fluid shear stress (FSS)•Resistance to FSS is a physiological, mechano-adaptive response in cancer cells•Cancer cells respond to FSS by activating the RhoA-myosin II axis and formins•Myosin II activity protects CTCs from hemodynamic forces in in vivo assays 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.

circulating tumor cells

fluid shear stress

formin

metastasis

myosin II

RhoA

Details

Title: Subtitle: Cancer Cells Resist Mechanical Destruction in Circulation via RhoA/Actomyosin-Dependent Mechano-Adaptation
Creators: Devon L Moose - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Benjamin L Krog - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Tae-Hyung Kim - Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA
Lei Zhao - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Sophia Williams-Perez - Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Gretchen Burke - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Lillian Rhodes - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Marion Vanneste - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Patrick Breheny - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA 52242, USA
Mohammed Milhem - Holden Comprehensive Cancer Center, Iowa City, IA 52242, USA
Christopher S Stipp - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Amy C Rowat - Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA
Michael D Henry - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.30(11), pp.3864-3874.e6
Publisher: Elsevier Inc
DOI: 10.1016/j.celrep.2020.02.080
PMID: 32187555
PMCID: PMC7219793
ISSN: 2211-1247
eISSN: 2211-1247
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100000001, name: National Science Foundation
Language: English
Date published: 03/17/2020
Academic Unit: Molecular Physiology and Biophysics; Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Biostatistics; Biology; Radiation Oncology; Urology; Internal Medicine
Record Identifier: 9984217541602771

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