CARM1 reprograms fatty acid metabolism to promote ovarian cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE202259 | GEO | 2023/03/29
REPOSITORIES: GEO
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Project description:CARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in cancers and stimulates growth. However, clinically applicable therapeutic strategies based on CARM1 expression in cancer remains to be explored. Here we show that epithelial ovarian cancer is among the cancers with the highest CARM1 amplification rates that predicates a shorter survival. Our unbiased screen show that CARM1-expressing ovarian cancer cells are selectively sensitive to the inhibition of EZH2, another epigenetic regulator that silences its target genes. Inhibition of EZH2 activity using a clinically applicable small molecule inhibitor significantly suppressed the growth of CARM1-expressing ovarian tumors in two xenograft models. The observed selectivity correlates with upregulation of EZH2 target genes in a CARM1-dependent manner. CARM1 promotes EZH2 dependent gene silencing by methylating BAF155 to alter the antagonism between EZH2 and BAF155. Together, these results indicate that pharmacological inhibition of EZH2 is a novel therapeutic strategy for CARM1-expressing cancers.
2018-03-02 | GSE95643 | GEO
Project description:CARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in cancers and stimulates growth. However, clinically applicable therapeutic strategies based on CARM1 expression in cancer remains to be explored. Here we show that epithelial ovarian cancer is among the cancers with the highest CARM1 amplification rates that predicates a shorter survival. Our unbiased screen show that CARM1-expressing ovarian cancer cells are selectively sensitive to the inhibition of EZH2, another epigenetic regulator that silences its target genes. Inhibition of EZH2 activity using a clinically applicable small molecule inhibitor significantly suppressed the growth of CARM1-expressing ovarian tumors in two xenograft models. The observed selectivity correlates with upregulation of EZH2 target genes in a CARM1-dependent manner. CARM1 promotes EZH2 dependent gene silencing by methylating BAF155 to alter the antagonism between EZH2 and BAF155. Together, these results indicate that pharmacological inhibition of EZH2 is a novel therapeutic strategy for CARM1-expressing cancers.
2018-03-02 | GSE95644 | GEO
Project description:The goal of the project was global identification of CARM1 substrates. Arginine methylation landscapes were profiled and compared in wild type and CARM1 knockout cells to determine in vivo substrates of CARM1.
2017-07-03 | PXD005871 | Pride
Project description:The goal of this study is to identify ERalpha-target genes affected by overexpression of the histone arginine methyltransferase CARM1 in breast cancer cells. The roles of CARM1 in ERalpha+ breast cancer was not well characterized. Therefore, we created a Dox inducible CARM1 overexpressing MCF7 cell line where CARM1 is overexpressed by 2 fold to determine the created a Dox-inducible CARM1 overexpressing MCF7 cells for evaluation of the global effects of CARM1 on Eralpha-target gene expression. MCF7-tet-on-CARM1 clone 13 were treated under 4 conditions: DMSO; Dox; E2 (10nM); Dox+E2. In Dox+E2 condition, cells were pre-treated with Dox for 5 days before treating with E2 for 4 hours. 3 biological replicates were included and total of 12 samples were analyzed.
2011-06-01 | E-GEOD-26454 | biostudies-arrayexpress
Project description:Cancer cells exploit adaptive responses such as endoplasmic reticulum (ER) stress to support their survival. ER stress response is mediated in part by the ER-localized transmembrane sensor IRE1α endoribonuclease and its substrate XBP1 to regulate XBP1 target gene expression. However, the mechanism that controls the IRE1α/XBP1 pathway remains poorly understood. CARM1 is an oncogene that is often overexpressed in a number of cancer types including ovarian cancer. Here we report that CARM1 determines ER stress response by controlling the IRE1α/XBP1 pathway. Genome-wide profiling revealed that CARM1 regulates XBP1 target gene expression during ER stress response. CARM1 directly interacts with XBP1. Inhibition of the IRE1α/XBP1 pathway was effective in ovarian cancer in a CARM1-dependent manner both in vitro and in vivo in orthotopic and patient-derived xenograft models. In addition, IRE1α inhibitor B-I09 synergizes with immune checkpoint blockade anti-PD1 antibody in an immunocompetent CARM1-expressing ovarian cancer model.
2021-08-11 | GSE157117 | GEO
Project description:Cancer cells exploit adaptive responses such as endoplasmic reticulum (ER) stress to support their survival. ER stress response is mediated in part by the ER-localized transmembrane sensor IRE1α endoribonuclease and its substrate XBP1 to regulate XBP1 target gene expression. However, the mechanism that controls the IRE1α/XBP1 pathway remains poorly understood. CARM1 is an oncogene that is often overexpressed in a number of cancer types including ovarian cancer. Here we report that CARM1 determines ER stress response by controlling the IRE1α/XBP1 pathway. Genome-wide profiling revealed that CARM1 regulates XBP1 target gene expression during ER stress response. CARM1 directly interacts with XBP1. Inhibition of the IRE1α/XBP1 pathway was effective in ovarian cancer in a CARM1-dependent manner both in vitro and in vivo in orthotopic and patient-derived xenograft models. In addition, IRE1α inhibitor B-I09 synergizes with immune checkpoint blockade anti-PD1 antibody in an immunocompetent CARM1-expressing ovarian cancer model.
2021-08-11 | GSE157116 | GEO
Project description:The goal of this study is to identify ERalpha-target genes affected by knocking down of the histone arginine methyltransferase CARM1 in MCF7 breast cancer cells. The roles of CARM1 in ERalpha+ breast cancer was not well characterized. Therefore, we created a Dox inducible CARM1 knockingdown MCF7 cell line where CARM1 is decreased to 20% of endogeneous level to determine the created a Dox-inducible CARM1shRNA overexpressing MCF7 cells for evaluation of the global effects of CARM1 on ERalpha-target gene expression. MCF7-tet-on-CARM1shRNA clone 1 were treated under 4 conditions: DMSO; Dox; E2 (10nM); Dox+E2. In Dox+E2 condition, cells were pre-treated with Dox for 5 days before treating with E2 for 4 hours. 3 biological replicates were included and total of 12 samples were analyzed.
2011-06-01 | E-GEOD-26259 | biostudies-arrayexpress
Project description:Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires the dual specificity established by CARM1 on chromatin and a key chromatin remodeler.
2024-07-17 | GSE209910 | GEO
Project description:Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires the dual specificity established by CARM1 on chromatin and a key chromatin remodeler.
2024-07-17 | GSE209909 | GEO
Project description:Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires the dual specificity established by CARM1 on chromatin and a key chromatin remodeler.
2024-07-17 | GSE208775 | GEO