Matrix Metalloproteinases: Regulators of the Tumor Microenvironment

http://basicmed.med.ncku.edu.tw/admin/up_img/990319-2.pdf

Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling

비만아 부모의 돌봄 경험: q 방법론

Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Despite intensive scrutiny in vitro, in cell culture and in animal models, the normal physiological roles of these extracellular proteases have been elusive. Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.

/pdf/matrix-metalloproteinases-and-the-regulation-of-tissue-3wk0irdopd.pdf

Matrix metalloproteinases and the regulation of tissue remodelling

The local microenvironment, or niche, of a cancer cell plays important roles in cancer development. A major component of the niche is the extracellular matrix (ECM), a complex network of macromolecules with distinctive physical, biochemical, and biomechanical properties. Although tightly controlled during embryonic development and organ homeostasis, the ECM is commonly deregulated and becomes disorganized in diseases such as cancer. Abnormal ECM affects cancer progression by directly promoting cellular transformation and metastasis. Importantly, however, ECM anomalies also deregulate behavior of stromal cells, facilitate tumor-associated angiogenesis and inflammation, and thus lead to generation of a tumorigenic microenvironment. Understanding how ECM composition and topography are maintained and how their deregulation influences cancer progression may help develop new therapeutic interventions by targeting the tumor niche.

/pdf/the-extracellular-matrix-a-dynamic-niche-in-cancer-21xcbo41km.pdf

The extracellular matrix: A dynamic niche in cancer progression

Bromine Is an Essential Trace Element for Assembly of Collagen IV Scaffolds in Tissue Development and Architecture

https://www.cell.com/developmental-cell/pdf/S1534-5807(02)00400-8.pdf

Drosophila Matrix Metalloproteinases Are Required for Tissue Remodeling, but Not Embryonic Development

The canonical Wnt/β-catenin pathway is an ancient and evolutionarily conserved signaling pathway that is required for the proper development of all metazoans, from the basal demosponge Amphimedon queenslandica to humans. Misregulation of Wnt signaling is implicated in many human diseases, making this pathway an intense area of research in industry as well as academia. In this review, we explore our current understanding of the molecular steps involved in the transduction of a Wnt signal. We will focus on how the critical Wnt pathway component, β-catenin, is in a "futile cycle" of constant synthesis and degradation and how this cycle is disrupted upon pathway activation. We describe the role of the Wnt pathway in major human cancers and in the control of stem cell self-renewal in the developing organism and in adults. Finally, we describe well-accepted criteria that have been proposed as evidence for the involvement of a molecule in regulating the canonical Wnt pathway.

/pdf/the-way-wnt-works-components-and-mechanism-2d8kwojzx7.pdf

The way Wnt works: Components and mechanism

Matrix metalloproteinases (MMPs) are extracellular proteases highly expressed at wound sites. However, the precise function of MMPs during reepithelialization in vivo has been elusive in mammalian models because of the high level of redundancy among the 24 mammalian MMPs. For this reason we used Drosophila melanogaster, whose genome encodes only two MMPs-one secreted type (Mmp1) and one membrane-anchored type (Mmp2)-to study the function and regulation of the secreted class of MMPs in vivo. In the absence of redundancy, we found that the Drosophila secreted MMP, Mmp1, is required in the epidermis to facilitate reepithelialization by remodeling the basement membrane, promoting cell elongation and actin cytoskeletal reorganization, and activating extracellular signal-regulated kinase signaling. In addition, we report that the jun N-terminal kinase (JNK) pathway upregulates Mmp1 expression after wounding, but that Mmp1 is expressed independent of the JNK pathway in unwounded epidermis. When the JNK pathway is ectopically activated to overexpress Mmp1, the rate of healing is accelerated in an Mmp1-dependent manner. A primary function of Mmp1, under the control of the JNK pathway, is to promote basement membrane repair, which in turn may permit cell migration and the restoration of a continuous tissue.

Andrea Page-McCaw

Papers

Matrix metalloproteinases and the regulation of tissue remodelling

Bromine Is an Essential Trace Element for Assembly of Collagen IV Scaffolds in Tissue Development and Architecture

Drosophila Matrix Metalloproteinases Are Required for Tissue Remodeling, but Not Embryonic Development

The way Wnt works: Components and mechanism

A secreted MMP is required for reepithelialization during wound healing