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Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):1925-1930. doi: 10.1073/pnas.1718177115. Epub 2018 Feb 5.

Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses.

Author information

1
Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
2
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218.
3
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218.
4
Institute for Advanced Sciences, CRNS UMR 5309, INSERM U1209, Institut Albert Bonniot, University Grenoble Alpes, Site Santé, 5588 Grenoble, France.
5
Institute for Bioengineering of Catalonia, Facultat de Medicina, Universitat de Barcelona and Ciber Enfermedades Respiratorias, 08028 Barcelona, Spain.
6
Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.
7
Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; miguel.valverde@upf.edu.

Abstract

Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. Piezo2 is needed by brain metastatic cells from breast cancer (MDA-MB-231-BrM2) to probe their physical environment as they anchor and pull on their surroundings or when confronted with confined migration through narrow pores. Piezo2-mediated Ca2+ influx activates RhoA to control the formation and orientation of SFs and focal adhesions (FAs). A possible mechanism for the Piezo2-mediated activation of RhoA involves the recruitment of the Fyn kinase to the cell leading edge as well as calpain activation. Knockdown of Piezo2 in BrM2 cells alters SFs, FAs, and nuclear translocation of YAP; a phenotype rescued by overexpression of dominant-positive RhoA or its downstream effector, mDia1. Consequently, hallmarks of cancer invasion and metastasis related to RhoA, actin cytoskeleton, and/or force transmission, such as migration, extracellular matrix degradation, and Serpin B2 secretion, were reduced in cells lacking Piezo2.

KEYWORDS:

RhoA; actin stress fibers; calcium signaling; cancer; mechanotransduction

PMID:
29432180
PMCID:
PMC5828612
DOI:
10.1073/pnas.1718177115
[Indexed for MEDLINE]
Free PMC Article

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