Similar Datasets
Project description:SMARCB1 knockdown in liver cancer cells
| PRJNA419313 | ENA
Project description:SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice. Profiling Smarcb1 dependent gene expression we find genes which are dependent on Smarcb1 expression to be enriched for ECM and cell adhesion functions. We identify Igfbp7, which is related to the insulin-like growth factor binding proteins family, as a downstream target of Smarcb1 transcriptional activity, and show that re-introduction of Igfbp7 alone can hinder tumor development. Two cancer cell lines, 167 and 365, derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice were re-infected with a retro-viral vector for Smarcb1 re-expression or an empty retro-viral vector as control. Total-RNA was collected 3 days post infection so as to enrich for direct targets of Smarcb1 transcriptionaly regulated genes
2013-12-31 | E-GEOD-46017 | biostudies-arrayexpress
Project description:The aim of this study is to analyze the change in genome wide expression levels in HAP1 cells upon loss of SMARCB1, SMARCA4 or both these genes together. The SMARCB1 and SMARCA4 genes were the hits from a genome wide screen involving genetrap mutagenesis to find new players that are involved in sensitivity to Doxorubicin (Dox). It was found that loss of SMARCB1 and SMARCA4 genes impart resistance in HAP1 cells to Dox. To validate this, the genes were knocked out in HAP1 cells with CRISPR-Cas9 technology. Gene expression levels in SMARCB1 null, SMARCA4 null and SMARCB1-SMARCA4 double null cells were compared to wildtype HAP1 cells using RNAseq. From these experiments it was found that SMARCB1 loss caused several fold increase in ABCB1 gene levels. ABCB1 is an efflux pump in cells responsible for flushing out many small-molecule drugs. Further analysis of this gene confirmed that ABCB1 was the main factor responsible for Dox resistance upon SMARCB1 loss. In total there are four different cell types with two replicates for each cell type. Therefore, 8 samples in total.
2016-08-22 | E-GEOD-75515 | biostudies-arrayexpress
Project description:To investigate the loss of SMARCB1 , a critical component of SWI/SNF complex in bladder cancer tumorigenesis and metastasis. We investigated the loss by generating SMARCB1 KO cells by CRISPR and rescuing the expression of SMARCB1 by lentivirus in the KO cell line. The cell lines were implanted orthotopically into bladder wall to investigate its effects on tumor growth and metastatic phenotype.
2023-11-15 | GSE212762 | GEO
Project description:Identifying the mechanism action of SMARCB1 in totally different cell lines. Determine whether it is general role or context dependent role.
2019-10-04 | GSE120831 | GEO
Project description:While oncogenes can potentially be inhibited with small molecules, the loss of tumor suppressors is more common and presents a conundrum for precision therapy because the proteins are no longer present. SMARCB1-mutant cancers epitomize this challenge because these highly lethal cancers are driven by inactivation of a single gene, a subunit of SWI/SNF chromatin remodeling complexes. To generate mechanistic insight into the consequences of SMARCB1 mutation and to seek vulnerabilities, we contributed 16 SMARCB1-mutant cell lines to a near-genomewide CRISPR screen as part of the Cancer Dependency Map1-3. Here we report that the little-studied gene DCAF5 (DDB1-CUL4 Associated Factor 5) is a specific dependency in SMARCB1-mutant cancers. We show that DCAF5 serves a quality control function for SWI/SNF complexes and in the absence of SMARCB1 DCAF5 causes degradation of incompletely assembled SWI/SNF complexes. Upon inhibition of DCAF5 SMARCB1-deficient SWI/SNF complexes re-accumulate, bind to target loci, and restore gene expression to levels sufficient to fully reverse the cancer state, including in a xenograft mouse model. Consequently, cancer results not from the loss of SMARCB1 function per se but rather from DCAF5-mediated degradation of SWI/SNF complexes. These data indicate that therapeutic targeting of DCAF5 may be sufficient to restore substantial SWI/SNF function and reverse cancer phenotypes caused by SMARCB1 loss.
2024-03-22 | GSE215024 | GEO
Project description:While oncogenes can potentially be inhibited with small molecules, the loss of tumor suppressors is more common and presents a conundrum for precision therapy because the proteins are no longer present. SMARCB1-mutant cancers epitomize this challenge because these highly lethal cancers are driven by inactivation of a single gene, a subunit of SWI/SNF chromatin remodeling complexes. To generate mechanistic insight into the consequences of SMARCB1 mutation and to seek vulnerabilities, we contributed 16 SMARCB1-mutant cell lines to a near-genomewide CRISPR screen as part of the Cancer Dependency Map1-3. Here we report that the little-studied gene DCAF5 (DDB1-CUL4 Associated Factor 5) is a specific dependency in SMARCB1-mutant cancers. We show that DCAF5 serves a quality control function for SWI/SNF complexes and in the absence of SMARCB1 DCAF5 causes degradation of incompletely assembled SWI/SNF complexes. Upon inhibition of DCAF5 SMARCB1-deficient SWI/SNF complexes re-accumulate, bind to target loci, and restore gene expression to levels sufficient to fully reverse the cancer state, including in a xenograft mouse model. Consequently, cancer results not from the loss of SMARCB1 function per se but rather from DCAF5-mediated degradation of SWI/SNF complexes. These data indicate that therapeutic targeting of DCAF5 may be sufficient to restore substantial SWI/SNF function and reverse cancer phenotypes caused by SMARCB1 loss.
2024-03-22 | GSE215023 | GEO
Project description:While oncogenes can potentially be inhibited with small molecules, the loss of tumor suppressors is more common and presents a conundrum for precision therapy because the proteins are no longer present. SMARCB1-mutant cancers epitomize this challenge because these highly lethal cancers are driven by inactivation of a single gene, a subunit of SWI/SNF chromatin remodeling complexes. To generate mechanistic insight into the consequences of SMARCB1 mutation and to seek vulnerabilities, we contributed 16 SMARCB1-mutant cell lines to a near-genomewide CRISPR screen as part of the Cancer Dependency Map1-3. Here we report that the little-studied gene DCAF5 (DDB1-CUL4 Associated Factor 5) is a specific dependency in SMARCB1-mutant cancers. We show that DCAF5 serves a quality control function for SWI/SNF complexes and in the absence of SMARCB1 DCAF5 causes degradation of incompletely assembled SWI/SNF complexes. Upon inhibition of DCAF5 SMARCB1-deficient SWI/SNF complexes re-accumulate, bind to target loci, and restore gene expression to levels sufficient to fully reverse the cancer state, including in a xenograft mouse model. Consequently, cancer results not from the loss of SMARCB1 function per se but rather from DCAF5-mediated degradation of SWI/SNF complexes. These data indicate that therapeutic targeting of DCAF5 may be sufficient to restore substantial SWI/SNF function and reverse cancer phenotypes caused by SMARCB1 loss.
2024-03-22 | GSE215022 | GEO
Project description:SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice. Profiling Smarcb1 dependent gene expression we find genes which are dependent on Smarcb1 expression to be enriched for ECM and cell adhesion functions. We identify Igfbp7, which is related to the insulin-like growth factor binding proteins family, as a downstream target of Smarcb1 transcriptional activity, and show that re-introduction of Igfbp7 alone can hinder tumor development.
2013-12-31 | GSE46017 | GEO
Project description:While oncogenes can potentially be inhibited with small molecules, the loss of tumor suppressors is more common and is problematic because the tumor suppressor proteins are no longer present to be targeted. Notable examples include SMARCB1-mutant cancers, which are highly lethal malignancies driven by the inactivation of a subunit of SWI/SNF chromatin remodeling complexes. To generate mechanistic insight into the consequences of SMARCB1 mutation and to identify vulnerabilities, we contributed 14 SMARCB1-mutant cell lines to a near genome-wide CRISPR screen as part of the Cancer Dependency Map Project1-3. Here, we report that the little-studied gene DDB1-CUL4 Associated Factor 5 (DCAF5) is required for the survival of SMARCB1-mutant cancers. We show that DCAF5 serves a quality control function for SWI/SNF complexes and promotes degradation of incompletely assembled SWI/SNF complexes in the absence of SMARCB1. Upon depletion of DCAF5, SMARCB1-deficient SWI/SNF complexes re-accumulate, bind to target loci, and restore SWI/SNF-mediated gene expression to levels sufficient to reverse the cancer state, including in vivo. Consequently, cancer results not from the loss of SMARCB1 function per se but rather from DCAF5-mediated degradation of SWI/SNF complexes. These data indicate that therapeutic targeting of ubiquitin-mediated quality control factors may effectively reverse the malignant state of some cancers driven by disruption of tumor suppressor complexes.
2024-01-21 | PXD046276 | Pride