Document Detail


Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway.
MedLine Citation:
PMID:  17496924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endoglin is a transforming growth factor beta (TGFbeta) superfamily auxiliary receptor. We had previously shown that it suppressed prostate cancer (PCa) cell motility, and that its expression was lost during PCa progression. The mechanism by which endoglin inhibits PCa cell motility is unknown. Here we demonstrate that endoglin abrogates TGFbeta-mediated cell motility, but does not alter cell surface binding of TGFbeta. By measuring Smad-specific phosphorylation and Smad-responsive promoter activity, endoglin was shown to constitutively activate Smad1, with little-to-no effect upon Smad3. Knockdown of Smad1 increased motility and abrogated endoglin's effects. As type I activin receptor-like kinases (ALKs) are necessary for Smad activation, we went on to show that knockdown of ALK2, but not TGFbetaRI (ALK5), abrogated endoglin-mediated decreases in cell motility and constitutively active ALK2 was sufficient to restore a low-motility phenotype in endoglin deficient cells. These findings provide the first evidence that endoglin decreases PCa cell motility through activation of the ALK2-Smad1 pathway.
Authors:
C S Craft; D Romero; C P H Vary; R C Bergan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-05-14
Journal Detail:
Title:  Oncogene     Volume:  26     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-09     Completed Date:  2008-01-29     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  7240-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Activin Receptors, Type I / physiology*
Antigens, CD / physiology*
Blotting, Western
Cell Line, Tumor
Cell Movement / physiology*
Flow Cytometry
Humans
Male
Prostatic Neoplasms / metabolism,  pathology*
Receptors, Cell Surface / physiology*
Reverse Transcriptase Polymerase Chain Reaction
Smad1 Protein / physiology*
Grant Support
ID/Acronym/Agency:
CA90386/CA/NCI NIH HHS; P20 RR015555/RR/NCRR NIH HHS; P20 RR015555-076459/RR/NCRR NIH HHS; P20 RR015555-076465/RR/NCRR NIH HHS; R01 HL083151/HL/NHLBI NIH HHS; R01 HL083151-01A2S1/HL/NHLBI NIH HHS; T32CA09560/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/ENG protein, human; 0/Receptors, Cell Surface; 0/SMAD1 protein, human; 0/Smad1 Protein; EC 2.7.11.30/ACVR1 protein, human; EC 2.7.11.30/Activin Receptors, Type I
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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