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rdf:type |
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lifeskim:mentions |
umls-concept:C0007589,
umls-concept:C0018270,
umls-concept:C0037083,
umls-concept:C0038250,
umls-concept:C0040690,
umls-concept:C0332453,
umls-concept:C0851827,
umls-concept:C1333665,
umls-concept:C1511938,
umls-concept:C1519697,
umls-concept:C1701901,
umls-concept:C1710082,
umls-concept:C2349975
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pubmed:issue |
19
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pubmed:dateCreated |
2011-5-11
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pubmed:abstractText |
Stem cell antigen (Sca)-1/Ly6A, a glycerophosphatidylinositol-linked surface protein, was found to be associated with murine stem cell- and progenitor cell-enriched populations, and also has been linked to the capacity of tumor-initiating cells. Despite these interesting associations, this protein's functional role in these processes remains largely unknown. To identify the mechanism underlying the protein's possible role in mammary tumorigenesis, Sca-1 expression was examined in Sca-1(+/EGFP) mice during carcinogenesis. Mammary tumor cells derived from these mice readily engrafted in syngeneic mice, and tumor growth was markedly inhibited on down-regulation of Sca-1 expression. The latter effect was associated with significantly elevated expression of the TGF-? ligand growth differentiation factor-10 (GDF10), which was found to selectively activate TGF-? receptor (T?RI/II)-dependent Smad3 phosphorylation. Overexpression of GDF10 attenuated tumor formation; conversely, silencing of GDF10 expression reversed these effects. Sca-1 attenuated GDF10-dependent TGF-? signaling by disrupting the heterodimerization of T?RI and T?RII receptors. These findings suggest a new functional role for Sca-1 in maintaining tumorigenicity, in part by acting as a potent suppressor of TGF-? signaling.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Ly,
http://linkedlifedata.com/resource/pubmed/chemical/Gdf10 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Differentiation Factor 10,
http://linkedlifedata.com/resource/pubmed/chemical/Ly6a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/TGF-beta type I receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/enhanced green fluorescent protein,
http://linkedlifedata.com/resource/pubmed/chemical/transforming growth factor-beta...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
108
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7820-5
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pubmed:dateRevised |
2011-11-10
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pubmed:meshHeading |
pubmed-meshheading:21518866-Animals,
pubmed-meshheading:21518866-Antigens, Ly,
pubmed-meshheading:21518866-Base Sequence,
pubmed-meshheading:21518866-Female,
pubmed-meshheading:21518866-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21518866-Green Fluorescent Proteins,
pubmed-meshheading:21518866-Growth Differentiation Factor 10,
pubmed-meshheading:21518866-Mammary Neoplasms, Experimental,
pubmed-meshheading:21518866-Membrane Proteins,
pubmed-meshheading:21518866-Mice,
pubmed-meshheading:21518866-Mice, Inbred C57BL,
pubmed-meshheading:21518866-Mice, Knockout,
pubmed-meshheading:21518866-Mice, Transgenic,
pubmed-meshheading:21518866-Models, Biological,
pubmed-meshheading:21518866-Protein-Serine-Threonine Kinases,
pubmed-meshheading:21518866-RNA, Messenger,
pubmed-meshheading:21518866-RNA, Neoplasm,
pubmed-meshheading:21518866-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:21518866-Signal Transduction,
pubmed-meshheading:21518866-Smad3 Protein,
pubmed-meshheading:21518866-Transforming Growth Factor beta
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pubmed:year |
2011
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pubmed:articleTitle |
Stem cell antigen-1 enhances tumorigenicity by disruption of growth differentiation factor-10 (GDF10)-dependent TGF-beta signaling.
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pubmed:affiliation |
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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