TY  - JOUR
AU  - Eschenbruch, Julian
AU  - Dreissen, Georg
AU  - Springer, Ronald
AU  - Konrad, Jens
AU  - Merkel, Rudolf
AU  - Hoffmann, Bernd
AU  - Noetzel, Erik
TI  - From Microspikes to Stress Fibers: Actin Remodeling in Breast Acini Drives Myosin II-Mediated Basement Membrane Invasion
JO  - Cells
VL  - 10
IS  - 8
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - FZJ-2021-03392
SP  - 1979 -
PY  - 2021
AB  - The cellular mechanisms of basement membrane (BM) invasion remain poorly understood. We investigated the invasion-promoting mechanisms of actin cytoskeleton reorganization in BM-covered MCF10A breast acini. High-resolution confocal microscopy has characterized actin cell protrusion formation and function in response to tumor-resembling ECM stiffness and soluble EGF stimulation. Traction force microscopy quantified the mechanical BM stresses that invasion-triggered acini exerted on the BM–ECM interface. We demonstrate that acini use non-proteolytic actin microspikes as functional precursors of elongated protrusions to initiate BM penetration and ECM probing. Further, these microspikes mechanically widened the collagen IV pores to anchor within the BM scaffold via force-transmitting focal adhesions. Pre-invasive basal cells located at the BM–ECM interface exhibited predominantly cortical actin networks and actin microspikes. In response to pro-invasive conditions, these microspikes accumulated and converted subsequently into highly contractile stress fibers. The phenotypical switch to stress fiber cells matched spatiotemporally with emerging high BM stresses that were driven by actomyosin II contractility. The activation of proteolytic invadopodia with MT1-MMP occurred at later BM invasion stages and only in cells already disseminating into the ECM. Our study demonstrates that BM pore-widening filopodia bridge mechanical ECM probing function and contractility-driven BM weakening. Finally, these EMT-related cytoskeletal adaptations are critical mechanisms inducing the invasive transition of benign breast acini.
LB  - PUB:(DE-HGF)16
C6  - pmid:34440749
UR  - <Go to ISI:>//WOS:000689047400001
DO  - DOI:10.3390/cells10081979
UR  - https://juser.fz-juelich.de/record/894790
ER  -