Next Article in Journal
The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma
Next Article in Special Issue
Nanomechanical Hallmarks of Helicobacter pylori Infection in Pediatric Patients
Previous Article in Journal
Genetic Architecture and Molecular, Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art, Opportunities and Challenges
Article

Cell Force-Driven Basement Membrane Disruption Fuels EGF- and Stiffness-Induced Invasive Cell Dissemination from Benign Breast Gland Acini

1
Institute of Biological Information Processing 2 (IBI-2): Mechanobiology, Forschungszentrum Jülich, 52425 Jülich, Germany
2
SUPA, School of Physics and Astronomy, University of St Andrews, St Andrews KY16 9SS, UK
3
Humboldt Centre for Nano- and Biophotonics, Department of Chemistry, Universität zu Köln, 50939 Köln, Germany
*
Author to whom correspondence should be addressed.
These authors share the first authorship.
Academic Editors: Katarzyna Pogoda and Stefano Leporatti
Int. J. Mol. Sci. 2021, 22(8), 3962; https://doi.org/10.3390/ijms22083962
Received: 12 March 2021 / Revised: 30 March 2021 / Accepted: 7 April 2021 / Published: 12 April 2021
Local basement membrane (BM) disruption marks the initial step of breast cancer invasion. The activation mechanisms of force-driven BM-weakening remain elusive. We studied the mechanical response of MCF10A-derived human breast cell acini with BMs of tuneable maturation to physical and soluble tumour-like extracellular matrix (ECM) cues. Traction force microscopy (TFM) and elastic resonator interference stress microscopy (ERISM) were used to quantify pro-invasive BM stress and protrusive forces. Substrate stiffening and mechanically impaired BM scaffolds induced the invasive transition of benign acini synergistically. Robust BM scaffolds attenuated this invasive response. Additional oncogenic EGFR activation compromised the BMs’ barrier function, fuelling invasion speed and incidence. Mechanistically, EGFR-PI3-Kinase downstream signalling modulated both MMP- and force-driven BM-weakening processes. We show that breast acini form non-proteolytic and BM-piercing filopodia for continuous matrix mechanosensation, which significantly push and pull on the BM and ECM under pro-invasive conditions. Invasion-triggered acini further shear and compress their BM by contractility-based stresses that were significantly increased (3.7-fold) compared to non-invasive conditions. Overall, the highest amplitudes of protrusive and contractile forces accompanied the highest invasiveness. This work provides a mechanistic concept for tumour ECM-induced mechanically misbalanced breast glands fuelling force-driven BM disruption. Finally, this could facilitate early cell dissemination from pre-invasive lesions to metastasize eventually. View Full-Text
Keywords: basement membrane; mechanobiology; mechanically driven cancer progression; mechanosensing; neoplasm invasion; breast cancer invasion; cell force; mechanosensory transduction; filopodia basement membrane; mechanobiology; mechanically driven cancer progression; mechanosensing; neoplasm invasion; breast cancer invasion; cell force; mechanosensory transduction; filopodia
Show Figures

Figure 1

MDPI and ACS Style

Gaiko-Shcherbak, A.; Eschenbruch, J.; Kronenberg, N.M.; Teske, M.; Wolters, B.; Springer, R.; Gather, M.C.; Merkel, R.; Hoffmann, B.; Noetzel, E. Cell Force-Driven Basement Membrane Disruption Fuels EGF- and Stiffness-Induced Invasive Cell Dissemination from Benign Breast Gland Acini. Int. J. Mol. Sci. 2021, 22, 3962. https://doi.org/10.3390/ijms22083962

AMA Style

Gaiko-Shcherbak A, Eschenbruch J, Kronenberg NM, Teske M, Wolters B, Springer R, Gather MC, Merkel R, Hoffmann B, Noetzel E. Cell Force-Driven Basement Membrane Disruption Fuels EGF- and Stiffness-Induced Invasive Cell Dissemination from Benign Breast Gland Acini. International Journal of Molecular Sciences. 2021; 22(8):3962. https://doi.org/10.3390/ijms22083962

Chicago/Turabian Style

Gaiko-Shcherbak, Aljona, Julian Eschenbruch, Nils M. Kronenberg, Michael Teske, Benjamin Wolters, Ronald Springer, Malte C. Gather, Rudolf Merkel, Bernd Hoffmann, and Erik Noetzel. 2021. "Cell Force-Driven Basement Membrane Disruption Fuels EGF- and Stiffness-Induced Invasive Cell Dissemination from Benign Breast Gland Acini" International Journal of Molecular Sciences 22, no. 8: 3962. https://doi.org/10.3390/ijms22083962

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop