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Traction forces mediated by alpha6beta4 integrin: implications for basement membrane organization and tumor invasion
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2001-12-12Keywords
Antigens, SurfaceBasement Membrane
Breast Neoplasms
Cell Adhesion
Extracellular Matrix
Humans
Integrin alpha6beta4
Integrins
Laminin
Microscopy, Electron
Microscopy, Fluorescence
Microscopy, Video
*Neoplasm Invasiveness
Neoplasms
Pseudopodia
Signal Transduction
Tumor Cells, Cultured
Cancer Biology
Neoplasms
Metadata
Show full item recordAbstract
The integrin alpha6beta4, a laminin receptor that stabilizes epithelial cell adhesion to the basement membrane (BM) through its association with cytokeratins, can stimulate the formation and stabilization of actin-rich protrusions in carcinoma cells. An important, unresolved issue, however, is whether this integrin can transmit forces to the substrate generated by the acto-myosin system. Using a traction-force detection assay, we detected forces exerted through alpha6beta4 on either laminin-1 or on an anti-alpha6 antibody, demonstrating that this integrin can transmit forces without the need to engage other integrins. These alpha6beta4-dependent traction forces were organized into a compression machine localized to the base of lamellae. We hypothesized that the compression forces generated by alpha6beta4 result in the remodeling of BMs because this integrin plays a major role in the interaction of epithelial and carcinoma cells with such structures. Indeed, we observed that carcinoma cells are able to remodel a reconstituted BM through alpha6beta4-mediated compression forces by a process that involves the packing of BM material under the cells and the mechanical removal of BM from adjacent areas. The distinct signaling functions of alpha6beta4, which activate phosphoinositide 3-OH kinase and RhoA, also contribute to remodeling. Importantly, we demonstrate remodeling of a native BM by epithelial cells and the involvement of alpha6beta4 in this remodeling. Our findings have important implications for the mechanism of both BM organization and tumor invasion.Source
Mol Biol Cell. 2001 Dec;12(12):4030-43.
DOI
10.1091/mbc.12.12.4030Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26244PubMed ID
11739798Related Resources
ae974a485f413a2113503eed53cd6c53
10.1091/mbc.12.12.4030