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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1925-1930 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 115 |
| Issue number | 8 |
| DOIs | |
| State | Published - Feb 20 2018 |
Fingerprint
Keywords
- Actin stress fibers
- Calcium signaling
- Cancer
- Mechanotransduction
- RhoA
ASJC Scopus subject areas
- General
Cite this
Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses. / Pardo-Pastor, Carlos; Rubio-Moscardo, Fanny; Vogel-González, Marina; Serra, Selma A.; Afthinos, Alexandros; Mrkonjic, Sanela; Destaing, Olivier; Abenza, Juan F.; Fernández-Fernández, José M.; Trepat, Xavier; Albiges-Rizo, Corinne; Konstantopoulos, K; Valverde, Miguel A.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 8, 20.02.2018, p. 1925-1930.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses
AU - Pardo-Pastor, Carlos
AU - Rubio-Moscardo, Fanny
AU - Vogel-González, Marina
AU - Serra, Selma A.
AU - Afthinos, Alexandros
AU - Mrkonjic, Sanela
AU - Destaing, Olivier
AU - Abenza, Juan F.
AU - Fernández-Fernández, José M.
AU - Trepat, Xavier
AU - Albiges-Rizo, Corinne
AU - Konstantopoulos, K
AU - Valverde, Miguel A.
PY - 2018/2/20
Y1 - 2018/2/20
N2 - 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.
AB - 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.
KW - Actin stress fibers
KW - Calcium signaling
KW - Cancer
KW - Mechanotransduction
KW - RhoA
UR - http://www.scopus.com/inward/record.url?scp=85042199307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042199307&partnerID=8YFLogxK
U2 - 10.1073/pnas.1718177115
DO - 10.1073/pnas.1718177115
M3 - Article
C2 - 29432180
AN - SCOPUS:85042199307
VL - 115
SP - 1925
EP - 1930
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 8
ER -