Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
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...This results in the recruitment of myeloid cells to 60 Cell 141, April 2, 2010 ©2010 Elsevier Inc. these sites (Erler et al., 2009), possibly owing to altered tissue stiffness (Levental et al., 2009)....
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3,486 citations
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...Notably, genetic or pharmacological blockade of lysyl oxidasemediated collagen crosslinking impedes late-stage cancer progression in mouse models of mammary carcinogenesis (Levental et al., 2009)....
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...…crosslinking of collagen fibrils (largely produced by CAFs) that imparts a proinvasive phenotype on mammary cancer cells, which is dependent on enhanced PI3 kinase (PI3K) signaling, and associated with integrin clustering and increased presence of focal adhesions (Levental et al., 2009)....
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3,190 citations
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...The stiffening of tumors is induced by ECM deposition and remodeling by resident fibroblasts, and by increased contractility of the transformed epithelium (Butcher et al., 2009; Levental et al., 2009)....
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...…fibers are reoriented and, thereafter, crosslinked by LOX and transglutaminase, thus generating larger, more-rigid fibrils that further stiffen the tissue ECM (Butcher et al., 2009; Erler and Weaver, 2009; Levental et al., 2009; Lucero and Kagan, 2006; Payne et al., 2007; Rodriguez et al., 2008)....
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...Thus collagen I gels are useful substrates to assess the role of collagen and FN stiffness, and organization on the pathogenesis of tumor progression and invasion (Levental et al., 2009; Provenzano et al., 2009)....
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