Source:http://linkedlifedata.com/resource/pubmed/id/18676838
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
|
pubmed:dateCreated |
2008-8-4
|
pubmed:abstractText |
Malignant rhabdoid tumors (MRT) are extremely aggressive pediatric tumors caused by the inactivation of the hSNF5/INI1 tumor suppressor gene, which encodes a core member of the SWI/SNF chromatin remodeling complex. Roles for hSNF5/INI1 in cell cycle and differentiation have been documented. Based on the observation that MRTs are highly invasive, we investigated a role for hSNF5/INI1 in cell migration. MRT cell lines exhibit high migration properties that are dramatically reduced upon hSNF5/INI1 expression. This effect is associated with the disorganization of the actin stress fiber network and is mediated by the inhibition of the activity of the small GTPase RhoA, through a nuclear, SWI/SNF-dependent transcriptional mechanism. We further show that the knockdown of hSNF5/INI1 in epithelial 293T or MCF7 cells results in increased cell size, loss of cell-cell adhesions, and enhanced migration, associated with an increased RhoA activity. Finally, we show that the SNF5 homology domain is required for hSNF5/INI1-mediated inhibition of migration, and that a missense mutation (S284L) associated with cancer is sufficient to impair hSNF5/INI1 function in migration. We conclude that the inhibition of migration is another crucial tumor suppressor function of hSNF5/INI1, in addition to its previously described functions in proliferation and differentiation, and that its loss-of-function in MRTs may account for the high invasiveness and metastatic potential of these tumors.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chromosomal Proteins, Non-Histone,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMARCB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein
|
pubmed:status |
MEDLINE
|
pubmed:month |
Aug
|
pubmed:issn |
1538-7445
|
pubmed:author | |
pubmed:issnType |
Electronic
|
pubmed:day |
1
|
pubmed:volume |
68
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
6154-61
|
pubmed:meshHeading |
pubmed-meshheading:18676838-Base Sequence,
pubmed-meshheading:18676838-Cell Line,
pubmed-meshheading:18676838-Cell Movement,
pubmed-meshheading:18676838-Chromosomal Proteins, Non-Histone,
pubmed-meshheading:18676838-DNA Primers,
pubmed-meshheading:18676838-DNA-Binding Proteins,
pubmed-meshheading:18676838-Fluorescent Antibody Technique,
pubmed-meshheading:18676838-Humans,
pubmed-meshheading:18676838-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:18676838-Transcription Factors,
pubmed-meshheading:18676838-rhoA GTP-Binding Protein
|
pubmed:year |
2008
|
pubmed:articleTitle |
RhoA-dependent regulation of cell migration by the tumor suppressor hSNF5/INI1.
|
pubmed:affiliation |
Institut Curie and Institut National de la Santé et de la Recherche Medicale U830, Unité de Génétique et Biologie des Cancers, Paris, France.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|