| Smad7 restricts melanoma invasion by restoring N-cadherin expression and establishing heterotypic cell-cell interactions in vivo. | |
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MedLine Citation:
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PMID: 20738806 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The list of transforming growth factor-beta (TGF-β)-related proteins in non-canonical TGF-β signaling is growing. Examples include receptor-Smads directing micro-RNA processing and inhibitory-Smads, e.g. Smad7, directing cell adhesion. Human skin grafts with fluorescently tagged melanoma cells revealed Smad7-expressing cells positioned themselves proximal to the dermal-epidermal junction and failed to form tumors, while control cells readily invaded and formed tumors within the dermis. Smad7 significantly inhibited β-catenin T41/S45 phosphorylation associated with degradation and induced a 4.5-fold increase in full-length N-cadherin. Cell adhesion assays confirmed a strong interaction between Smad7-expressing cells and primary dermal fibroblasts mediated via N-cadherin, while control cells were incapable of such interaction. Immunofluorescent analysis of skin grafts indicated N-cadherin homotypic interaction at the surface of both Smad7 cells and primary dermal fibroblasts, in contrast to control melanoma cells. We propose that Smad7 suppresses β-catenin degradation and promotes interaction with N-cadherin, stabilizing association with neighboring dermal fibroblasts, thus mitigating invasion. |
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Authors:
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Kyle A DiVito; Valerie A Trabosh; You-Shin Chen; Yu Chen; Chris Albanese; Delphine Javelaud; Alain Mauviel; Cynthia M Simbulan-Rosenthal; Dean S Rosenthal |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-08-25 |
Journal Detail:
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Title: Pigment cell & melanoma research Volume: 23 ISSN: 1755-148X ISO Abbreviation: Pigment Cell Melanoma Res Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-10-26 Completed Date: 2011-02-04 Revised Date: 2012-08-16 |
Medline Journal Info:
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Nlm Unique ID: 101318927 Medline TA: Pigment Cell Melanoma Res Country: England |
Other Details:
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Languages: eng Pagination: 795-808 Citation Subset: IM |
Affiliation:
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Department of Biochemistry & Molecular Biology, Georgetown University School of Medicine Washington, DC, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD
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metabolism* Cadherins / metabolism* Cell Communication* Cell Line, Tumor Dermis / metabolism, pathology Disease Progression Green Fluorescent Proteins / metabolism Humans Keratinocytes / metabolism Male Melanoma / metabolism*, pathology* Models, Biological Neoplasm Invasiveness Skin Neoplasms / metabolism*, pathology* Skin Transplantation Smad7 Protein / metabolism* beta Catenin / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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1R01CA100443-01A1/CA/NCI NIH HHS; R01 CA100443-01A1/CA/NCI NIH HHS; R01 CA100443-02/CA/NCI NIH HHS; R01 CA100443-03/CA/NCI NIH HHS; R01 CA100443-04/CA/NCI NIH HHS; R01 CA100443-05/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/CDH2 protein, human; 0/Cadherins; 0/SMAD7 protein, human; 0/Smad7 Protein; 0/beta Catenin; 147336-22-9/Green Fluorescent Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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