Journal article
Brief pulses of high-level fluid shear stress enhance metastatic potential and rapidly alter the metabolism of cancer cells
Cell reports (Cambridge), Vol.45(2), 116908
02/24/2026
DOI: 10.1016/j.celrep.2025.116908
PMCID: PMC13034112
PMID: 41642710
Abstract
Circulating tumor cells (CTCs) face challenges to their survival, including mechanical and oxidative stresses that are different from cancer cells in solid primary and metastatic tumors. The impact of adaptations to the fluid microenvironment of the circulation on the outcome of the metastatic cascade is not well understood. Here, we find that cancer cells exposed to brief pulses of high-level fluid shear stress (FSS) exhibit enhanced invasiveness and anchorage-independent proliferation in vitro and enhanced metastatic colonization/tumor formation in vivo. Cancer cells exposed to FSS rapidly alter their metabolism in a manner that promotes survival by providing energy for cytoskeletal remodeling and contractility as well as reducing equivalents to counter oxidative stress associated with cell detachment. Thus, exposure to FSS may provide CTCs with an unexpected survival benefit that promotes metastatic colonization.
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•Brief pulses of fluid shear stress induce phenotypes associated with increased metastasis•Fluid shear stress induces a switch to oxidative metabolism•Cancer cells exposed to fluid shear stress show reduced levels of reactive oxygen species•Fluid shear stress rapidly activates folate metabolism, which protects cancer cells
Cancer cells are exposed to elevated fluid shear stress for brief periods during their journey through the circulation. Fluid shear stress exposure triggers rapid transcriptional and metabolic changes that protect cancer cells from oxidative stress and promote productive metastatic colonization.
Details
- Title: Subtitle
- Brief pulses of high-level fluid shear stress enhance metastatic potential and rapidly alter the metabolism of cancer cells
- Creators
- Amanda N. Pope - University of IowaDevon L. Moose - University of IowaGuy O. Hudson - University of IowaHank R. Weresh - University of IowaMarion R. Dykstra - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAAabha Y. Joshi - University of IowaPatrick Breheny - University of IowaEric B. Taylor - University of IowaMichael 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.45(2), 116908
- DOI
- 10.1016/j.celrep.2025.116908
- PMID
- 41642710
- PMCID
- PMC13034112
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Grant note
- NIH: R01DK138664, DK104998, R01CA263550 Sato Metastasis Research Fund
We thank Eric Weatherford for insight and guidance on OCR analysis. We thank the staff and facilities of the Radiation and Free Radical Research Core, the Metabolic Phenotyping Core, the Metabolomics Core, and the Flow Cytometry Facility for their assistance and training. This work was supported by NIH awards R01DK138664 and DK104998 to E.B.T. and R01CA263550 to M.D.H. A.N.P. was supported by T32CA078586, and D.L.M. was supported by T32GM0677954. Core facilities at the University of Iowa were supported in part by grant P30 CA086862 to the Holden Comprehensive Cancer Center. This research was also supported by a kind gift from the Sato Metastasis Research Fund.
- Language
- English
- Date published
- 02/24/2026
- Academic Unit
- Molecular Physiology and Biophysics; Biostatistics; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9985139480102771
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