Document Detail

Smad7 restricts melanoma invasion by restoring N-cadherin expression and establishing heterotypic cell-cell interactions in vivo.
MedLine Citation:
PMID:  20738806     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-25
Journal Detail:
Title:  Pigment cell & melanoma research     Volume:  23     ISSN:  1755-148X     ISO Abbreviation:  Pigment Cell Melanoma Res     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-26     Completed Date:  2011-02-04     Revised Date:  2014-10-02    
Medline Journal Info:
Nlm Unique ID:  101318927     Medline TA:  Pigment Cell Melanoma Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  795-808     Citation Subset:  IM    
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MeSH Terms
Antigens, CD / metabolism*
Cadherins / metabolism*
Cell Communication*
Cell Line, Tumor
Dermis / metabolism,  pathology
Disease Progression
Green Fluorescent Proteins / metabolism
Keratinocytes / metabolism
Melanoma / metabolism*,  pathology*
Models, Biological
Neoplasm Invasiveness
Skin Neoplasms / metabolism*,  pathology*
Skin Transplantation
Smad7 Protein / metabolism*
beta Catenin / metabolism
Grant Support
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; R01 CA129003/CA/NCI NIH HHS
Reg. No./Substance:
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

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