Document Detail

RAP1GAP inhibits cytoskeletal remodeling and motility in thyroid cancer cells.
MedLine Citation:
PMID:  22696507     Owner:  NLM     Status:  MEDLINE    
The functional significance of decreased RAP1GAP protein expression in human tumors is unclear. To identify targets of RAP1GAP downregulation in the thyroid gland, RAP1 and RAP2 protein expression in human thyroid cells and in primary thyroid tumors were analyzed. RAP1GAP and RAP2 were co-expressed in normal thyroid follicular cells. Intriguingly, RAP1 was not detected in normal thyroid cells, although it was detected in papillary thyroid carcinomas, which also expressed RAP2. Both RAP proteins were detected at the membrane in papillary thyroid tumors, suggesting that they are activated when RAP1GAP is downregulated. To explore the functional significance of RAP1GAP depletion, RAP1GAP was transiently expressed at the lowest level that is sufficient to block endogenous RAP2 activity in papillary and anaplastic thyroid carcinoma cell lines. RAP1GAP impaired the ability of cells to spread and migrate on collagen. Although RAP1GAP had no effect on protein tyrosine phosphorylation in growing cells, RAP1GAP impaired phosphorylation of focal adhesion kinase and paxillin at sites phosphorylated by SRC in cells acutely plated on collagen. SRC activity was increased in suspended cells, where it was inhibited by RAP1GAP. Inhibition of SRC kinase activity impaired cell spreading and motility. These findings identify SRC as a target of RAP1GAP depletion and suggest that the downregulation of RAP1GAP in thyroid tumors enhances SRC-dependent signals that regulate cellular architecture and motility.
Xiaoyun Dong; Waixing Tang; Stephen Stopenski; Marcia S Brose; Christopher Korch; Judy L Meinkoth
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-22
Journal Detail:
Title:  Endocrine-related cancer     Volume:  19     ISSN:  1479-6821     ISO Abbreviation:  Endocr. Relat. Cancer     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-23     Completed Date:  2012-11-13     Revised Date:  2013-08-13    
Medline Journal Info:
Nlm Unique ID:  9436481     Medline TA:  Endocr Relat Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  575-88     Citation Subset:  IM    
Department of Pharmacology - Head and Neck Surgery, School of Medicine, University of Pennsylvania, 421 Curie Boulevard, BRB II/III, Philadelphia, PA 19104, USA.
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MeSH Terms
Carcinoma, Papillary / genetics,  metabolism,  pathology*
Cell Line, Tumor
Cell Movement* / genetics,  physiology
Cytoskeleton / metabolism,  physiology*
Down-Regulation / genetics
GTPase-Activating Proteins / genetics,  metabolism,  physiology*
Gene Expression Regulation, Neoplastic
HT29 Cells
Proto-Oncogene Proteins pp60(c-src) / genetics,  metabolism,  physiology
Thyroid Neoplasms / genetics,  metabolism,  pathology*
rap GTP-Binding Proteins / genetics,  metabolism
rap1 GTP-Binding Proteins / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/GTPase-Activating Proteins; 0/RAP1GAP protein, human; EC Proteins pp60(c-src); EC 3.6.1.-/RAP2A protein, human; EC GTP-Binding Proteins; EC GTP-Binding Proteins

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