| Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway. | |
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MedLine Citation:
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PMID: 17496924 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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C S Craft; D Romero; C P H Vary; R C Bergan |
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Publication Detail:
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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:
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Title: Oncogene Volume: 26 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2007 Nov |
Date Detail:
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Created Date: 2007-11-09 Completed Date: 2008-01-29 Revised Date: 2011-02-10 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 7240-50 Citation Subset: IM |
Affiliation:
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Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical School, Northwestern University and the Robert H Lurie Cancer Center of Northwestern University, Chicago, IL, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Activin Receptors, Type I
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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:
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CA90386/CA/NCI NIH HHS; P20 RR015555-076459/RR/NCRR NIH HHS; P20 RR015555-076465/RR/NCRR NIH HHS; R01 HL083151-01A2S1/HL/NHLBI NIH HHS; T32CA09560/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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