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Nat Commun. 2017 Jan 18;8:14122. doi: 10.1038/ncomms14122.

Fluid shear stress activates YAP1 to promote cancer cell motility.

Author information

1
Children's Regenerative Medicine Program, Department of Pediatric Surgery, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
2
Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
3
Department of BioSciences, Rice University, Houston, Texas 77030, USA.
4
Department of Pathology, The University of Texas Medical School, Houston, Texas 77030, USA.
5
Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
6
Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.

Abstract

Mechanical stress is pervasive in egress routes of malignancy, yet the intrinsic effects of force on tumour cells remain poorly understood. Here, we demonstrate that frictional force characteristic of flow in the lymphatics stimulates YAP1 to drive cancer cell migration; whereas intensities of fluid wall shear stress (WSS) typical of venous or arterial flow inhibit taxis. YAP1, but not TAZ, is strictly required for WSS-enhanced cell movement, as blockade of YAP1, TEAD1-4 or the YAP1-TEAD interaction reduces cellular velocity to levels observed without flow. Silencing of TEAD phenocopies loss of YAP1, implicating transcriptional transactivation function in mediating force-enhanced cell migration. WSS dictates expression of a network of YAP1 effectors with executive roles in invasion, chemotaxis and adhesion downstream of the ROCK-LIMK-cofilin signalling axis. Altogether, these data implicate YAP1 as a fluid mechanosensor that functions to regulate genes that promote metastasis.

PMID:
28098159
PMCID:
PMC5253685
DOI:
10.1038/ncomms14122
[Indexed for MEDLINE]
Free PMC Article

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