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- W4361246077 abstract "<div>Abstract<p>Malignant rhabdoid tumors (MRT) are extremely aggressive pediatric tumors caused by the inactivation of the <i>hSNF5/INI1</i> tumor suppressor gene, which encodes a core member of the SWI/SNF chromatin remodeling complex. Roles for <i>hSNF5/INI1</i> in cell cycle and differentiation have been documented. Based on the observation that MRTs are highly invasive, we investigated a role for <i>hSNF5/INI1</i> in cell migration. MRT cell lines exhibit high migration properties that are dramatically reduced upon <i>hSNF5/INI1</i> 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 <i>hSNF5/INI1</i> 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 <i>hSNF5/INI1</i>, 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. [Cancer Res 2008;68(15):6154–61]</p></div>" @default.
- W4361246077 created "2023-03-31" @default.
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- W4361246077 date "2023-03-30" @default.
- W4361246077 modified "2023-10-17" @default.
- W4361246077 title "Data from RhoA-Dependent Regulation of Cell Migration by the Tumor Suppressor <i>hSNF5/INI1</i>" @default.
- W4361246077 doi "https://doi.org/10.1158/0008-5472.c.6497189" @default.
- W4361246077 hasPublicationYear "2023" @default.
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