Fibronectins, Their Fibrillogenesis, and In Vivo Functions

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Cold Spring Harbor perspectives in biology (Impact Factor: 8.68). 05/2011; 3(7). DOI: 10.1101/cshperspect.a005041
Source: PubMed


Fibronectin (FN) is a multidomain protein with the ability to bind simultaneously to cell surface receptors, collagen, proteoglycans, and other FN molecules. Many of these domains and interactions are also involved in the assembly of FN dimers into a multimeric fibrillar matrix. When, where, and how FN binds to its various partners must be controlled and coordinated during fibrillogenesis. Steps in the process of FN fibrillogenesis including FN self-association, receptor activities, and intracellular pathways have been under intense investigation for years. In this review, the domain organization of FN including the extra domains and variable region that are controlled by alternative splicing are described. We discuss how FN-FN and cell-FN interactions play essential roles in the initiation and progression of matrix assembly using complementary results from cell culture and embryonic model systems that have enhanced our understanding of this process.

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Available from: Jean E Schwarzbauer, Sep 29, 2015
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    • "Modification with fibronectin can be used to study effects of cell attachment. Fibronectin (Fn) is an extracellular glycoprotein that binds both cell integrins and other ECM molecules, and plays a major role in cell adhesion, growth and differentiation [42]. This glycoprotein is also important for neural development by promoting cell survival, migration, neurite outgrowth and synapse formation [43]. "
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    Biomaterials 03/2014; 35(16). DOI:10.1016/j.biomaterials.2014.02.039 · 8.56 Impact Factor
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    • "Normally it is integrins (cell membrane protein) that connect cells, including prostatic epithelial cells, to the ECM by binding to fibronectin already present in the matrix 47. This interaction is required for proper assembly of fibronectin in the matrix, something that is very important for ECM organization and stability 48, 49. Cancer typically involves an epithelial to mesenchymal transition (EMT), whereby malignant cells can now break loose of their defined position within the microenvironment. "
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    ABSTRACT: Globally, Prostate cancer (PCa) is the most frequently occurring non-cutaneous cancer, and is the second highest cause of cancer mortality in men. Serum prostate specific antigen (PSA) has been the standard in PCa screening since its approval by the American Food & Drug Administration (FDA) in 1994. Currently, PSA is used as an indicator for PCa - patients with a serum PSA level above 4ng/mL will often undergo prostate biopsy to confirm cancer. Unfortunately fewer than ~30% of these men will biopsy positive for cancer, meaning that the majority of men undergo invasive biopsy with little benefit. Despite PSA's notoriously poor specificity (33%), there is still a significant lack of credible alternatives. Therefore an ideal biomarker that can specifically detect PCa at an early stage is urgently required. The aim of this study was to investigate the potential of using deregulation of urinary proteins in order to detect Prostate Cancer (PCa) among Benign Prostatic Hyperplasia (BPH). To identify the protein signatures specific for PCa, protein expression profiling of 8 PCa patients, 12 BPH patients and 10 healthy males was carried out using LC-MS/MS. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This approach revealed that significant the down-regulation of Fibronectin and TP53INP2 was a characteristic event among PCa patients. Fibronectin mRNA down-regulation, was identified as offering improved specificity (50%) over PSA, albeit with a slightly lower although still acceptable sensitivity (75%) for detecting PCa. As for TP53INP2 on the other hand, its down-regulation was moderately sensitive (75%), identifying many patients with PCa, but was entirely non-specific (7%), designating many of the benign samples as malignant and being unable to accurately identify more than one negative.
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    • "Eight proteins have a Fibronectin like domain3 at the N-terminus. Fibronectin (FN) is a multidomain protein with the ability to bind simultaneously to cell surface receptors, collagen, proteoglycans, and other FN molecules (Schwarzbauer and De Simone, 2011). The phylogenetic tree is described in Figure 4B. "
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