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Title: | Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses |
Author: | Pardo Pastor, Carlos Rubio Moscardo, Fanny Vogel González, Marina Serra, Selma Angèlica Afthinos, Alexandros Mrkonjic, Sanela Destaing, Olivier Abenza, Juan F. Fernández Fernández, José M. Trepat Guixer, Xavier Albiges Rizo, Corinne Konstantopoulos, Konstantinos Valverde, Miguel Ángel |
Keywords: | Citosquelet Migració cel·lular Canals iònics Cytoskeleton Cell migration Ion channels |
Issue Date: | 20-Feb-2018 |
Publisher: | National Academy of Sciences |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1073/pnas.1718177115 |
It is part of: | Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2018, vol. 115, num. 8, p. 1925-1930 |
URI: | http://hdl.handle.net/2445/155235 |
Related resource: | https://doi.org/10.1073/pnas.1718177115 |
ISSN: | 0027-8424 |
Appears in Collections: | Articles publicats en revistes (Biomedicina) |
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