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From Microspikes to Stress Fibers: Actin Remodeling in Breast Acini Drives Myosin II-Mediated Basement Membrane Invasion

Institute of Biological Information Processing 2 (IBI-2): Mechanobiology, Forschungszentrum Jülich, 52428 Jülich, Germany
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Author to whom correspondence should be addressed.
Academic Editors: Rudolf E. Leube and Alexander E. Kalyuzhny
Cells 2021, 10(8), 1979; https://doi.org/10.3390/cells10081979
Received: 30 June 2021 / Revised: 22 July 2021 / Accepted: 27 July 2021 / Published: 4 August 2021
(This article belongs to the Special Issue Epithelial Cell Mechanics: From Physiology to Pathology)
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. View Full-Text
Keywords: filopodia; invadopodia; focal adhesion; basement membrane disruption; breast cancer invasion; actomyosin; cell force; mechanical probing; epithelial mechanobiology filopodia; invadopodia; focal adhesion; basement membrane disruption; breast cancer invasion; actomyosin; cell force; mechanical probing; epithelial mechanobiology
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MDPI and ACS Style

Eschenbruch, J.; Dreissen, G.; Springer, R.; Konrad, J.; Merkel, R.; Hoffmann, B.; Noetzel, E. From Microspikes to Stress Fibers: Actin Remodeling in Breast Acini Drives Myosin II-Mediated Basement Membrane Invasion. Cells 2021, 10, 1979. https://doi.org/10.3390/cells10081979

AMA Style

Eschenbruch J, Dreissen G, Springer R, Konrad J, Merkel R, Hoffmann B, Noetzel E. From Microspikes to Stress Fibers: Actin Remodeling in Breast Acini Drives Myosin II-Mediated Basement Membrane Invasion. Cells. 2021; 10(8):1979. https://doi.org/10.3390/cells10081979

Chicago/Turabian Style

Eschenbruch, Julian, Georg Dreissen, Ronald Springer, Jens Konrad, Rudolf Merkel, Bernd Hoffmann, and Erik Noetzel. 2021. "From Microspikes to Stress Fibers: Actin Remodeling in Breast Acini Drives Myosin II-Mediated Basement Membrane Invasion" Cells 10, no. 8: 1979. https://doi.org/10.3390/cells10081979

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