RT Journal Article
SR Electronic
T1 <em>α</em>-actinin-4 drives invasiveness by regulating myosin IIB expression and myosin IIA localization
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.12.426368
DO 10.1101/2021.01.12.426368
A1 Amlan Barai
A1 Abhishek Mukherjee
A1 Alakesh Das
A1 Neha Saxena
A1 Shamik Sen
YR 2021
UL http://biorxiv.org/content/early/2021/01/12/2021.01.12.426368.abstract
AB The mechanisms by which the mechanoresponsive actin crosslinking protein α-actinin-4 (ACTN4) regulates cell motility and invasiveness remains incompletely understood. Here we show that in addition to regulating protrusion dynamics and focal adhesion formation, ACTN4 transcriptionally regulates expression of non-muscle myosin IIB (NMM IIB), which is essential for mediating nuclear translocation during 3D invasion. We further demonstrate association between NMM IIA and ACTN4 at the cell front ensures retention of NMM IIA at the cell periphery. A protrusion-dependent model of confined migration recapitulating experimental observations predicts a dependence of protrusion forces on the degree of confinement and on the ratio of nucleus to matrix stiffness. Together, our results suggest that ACTN4 is a master regulator of cancer invasion that regulates invasiveness by controlling NMM IIB expression and NMM IIA localization.Competing Interest StatementThe authors have declared no competing interest.