Remodelling the extracellular matrix in development and disease

Bonnans, Caroline; Chou, Jonathan; Werb, Zena

doi:10.1038/nrm3904

Cited by 3,332 publications

(3,075 citation statements)

References 165 publications

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“…For example, it has been shown that traction forces exerted by cells on the ECM expose cryptic domains within collagen and fibronectin that can stimulate intracellular signaling pathways affecting cellular growth and ECM turnover (Hocking & Kowalski, 2002; Vogel & Sheetz, 2009; Orgel et al ., 2011; Bonnans et al ., 2014). The actin myosin cytoskeleton is the primary source of force generation by cells.…”

Section: Discussionmentioning

confidence: 99%

Reduction of fibroblast size/mechanical force down‐regulates TGF ‐β type II receptor: implications for human skin aging

et al. 2015

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SummaryThe structural integrity of human skin is largely dependent on the quality of the dermal extracellular matrix (ECM), which is produced, organized, and maintained by dermal fibroblasts. Normally, fibroblasts attach to the ECM and thereby achieve stretched, elongated morphology. A prominent characteristic of dermal fibroblasts in aged skin is reduced size, with decreased elongation and a more rounded, collapsed morphology. Here, we show that reduced size of fibroblasts in mechanically unrestrained three‐dimensional collagen lattices coincides with reduced mechanical force, measured by atomic force microscopy. Reduced size/mechanical force specifically down‐regulates TGF‐β type II receptor (TβRII) and thus impairs TGF‐β/Smad signaling pathway. Both TβRII mRNA and protein were decreased, resulting in 90% loss of TGF‐β binding to fibroblasts. Down‐regulation of TβRII was associated with significantly decreased phosphorylation, DNA‐binding, and transcriptional activity of its key downstream effector Smad3 and reduced expression of Smad3‐regulated essential ECM components type I collagen, fibronectin, and connective tissue growth factor (CTGF/CCN2). Restoration of TβRII significantly increased TGF‐β induction of Smad3 phosphorylation and stimulated expression of ECM components. Reduced expression of TβRII and ECM components in response to reduced fibroblast size/mechanical force was fully reversed by restoring size/mechanical force. Reduced fibroblast size was associated with reduced expression of TβRII and diminished ECM production, in aged human skin. Taken together, these data reveal a novel mechanism that provides a molecular basis for loss of dermal ECM, with concomitant increased fragility, which is a prominent feature of human skin aging.

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Section: Discussionmentioning

confidence: 99%

Reduction of fibroblast size/mechanical force down‐regulates TGF ‐β type II receptor: implications for human skin aging

et al. 2015

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“…The extracellular matrix provides on one hand the substrate for cell adhesion and traction, but on the other hand acts as physical barrier for invading cells [114]. Contact-dependent remodeling of the extracellular matrix hence determines rate and speed of cell migration along and through the extracellular matrix [115].…”

Section: Trafficking Of Other Cell Surface Adhesions Proteinsmentioning

confidence: 99%

“…Contact-dependent remodeling of the extracellular matrix hence determines rate and speed of cell migration along and through the extracellular matrix [115]. To achieve extracellular matrix remodeling, mesenchymal cells, such as solid tumor cells and fibroblasts, have developed a strategy to pericellularly remodel and proteolytically degrade the extracellular matrix using matrix metalloproteinases (MMPs) [114]. Cancer cells were shown to coordinate mechanotransduction and extracellular matrix remodeling by segregating the anterior force-generating leading edge containing integrins, F-actin and the membrane type 1 (MT1)-MMP from the posterior proteolytic zone where extracellular matrix fibers are cleaved [116].…”

Section: Trafficking Of Other Cell Surface Adhesions Proteinsmentioning

confidence: 99%

On the move: endocytic trafficking in cell migration

Maritzen

Schachtner

Legler

2015

Cell. Mol. Life Sci.

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Directed cell migration is a fundamental process underlying diverse physiological and pathophysiological phenomena ranging from wound healing and induction of immune responses to cancer metastasis. Recent advances reveal that endocytic trafficking contributes to cell migration in multiple ways. (1) At the level of chemokines and chemokine receptors: internalization of chemokines by scavenger receptors is essential for shaping chemotactic gradients in tissue, whereas endocytosis of chemokine receptors and their subsequent recycling is key for maintaining a high responsiveness of migrating cells. (2) At the level of integrin trafficking and focal adhesion dynamics: endosomal pathways do not only modulate adhesion by delivering integrins to their site of action, but also by supplying factors for focal adhesion disassembly. (3) At the level of extracellular matrix reorganization: endosomal transport contributes to tumor cell migration not only by targeting integrins to invadosomes but also by delivering membrane type 1 matrix metalloprotease to the leading edge facilitating proteolysis-dependent chemotaxis. Consequently, numerous endocytic and endosomal factors have been shown to modulate cell migration. In fact key modulators of endocytic trafficking turn out to be also key regulators of cell migration. This review will highlight the recent progress in unraveling the contribution of cellular trafficking pathways to cell migration.

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“…The invasion of malignant tumors requires the proteolytic degradation of extracellular matrix (ECM) components. Although many proteolytic enzymes and proteases have been implicated in matrix degradation, MMPs are most closely associated with the process of tumor invasion and metastasis (46,47). MMP2, a 72-kDa type IV collagenase also known as gelatinase A, is significantly increased in metastatic melanoma (43%) compared to normal (5%) tissue.…”

Section: Discussionmentioning

confidence: 99%

Lentiviral-mediated overexpression of long non-coding RNA GAS5 reduces invasion by mediating MMP2 expression and activity in human melanoma cells

Chen

Yang

et al. 2016

International Journal of Oncology

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Abstract. The present study evaluated the effects of long non-coding RNA GAS5 on the migration and invasion of melanoma cells. Using the SK-Mel-110 melanoma cell line, we stably expressed GAS5, visualized the distribution of GAS5 by RNA fluorescence in situ hybridization (FISH) and examined changes in cell migration and invasion with Transwell assays. In GAS5 overexpressed SK-Mel-110 cells, migrated and invaded cells decreased by 65.3 and 55.6%, respectively. Moreover, the MMP2 protein level, and its activity was downregulated by 67.9 and 15.8%, respectively. Overexpressing lncRNA GAS5 inhibited the migration and invasion ability of melanoma SK-Mel-110 cells, partially by decreasing the MMP2 expression and its activity. This study is the first to reveal a potential relationship between lncRNA GAS5 and the migration and invasion of melanoma.

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Remodelling the extracellular matrix in development and disease

Cited by 3,332 publications

References 165 publications

Reduction of fibroblast size/mechanical force down‐regulates TGF ‐β type II receptor: implications for human skin aging

Reduction of fibroblast size/mechanical force down‐regulates TGF ‐β type II receptor: implications for human skin aging

On the move: endocytic trafficking in cell migration

Lentiviral-mediated overexpression of long non-coding RNA GAS5 reduces invasion by mediating MMP2 expression and activity in human melanoma cells

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