Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA284577 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that TNBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing a novel kinase inhibitor and CRISPR/Cas9-mediated gene editing, we show here that triple-negative but not ER/PR+ breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. TNBC cells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An “Achilles cluster” of TNBC-specific genes are extremely sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in TNBC and CDK7 inhibition may be useful therapy for this challenging cancer. Expression microarrays in H3K27ac in triple-negative breast cancer +/- treatment with covalent CDK7 inhibitor THZ1 treatment
2015-09-24 | E-GEOD-69106 | biostudies-arrayexpress
Project description:Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that TNBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing a novel kinase inhibitor and CRISPR/Cas9-mediated gene editing, we show here that triple-negative but not ER/PR+ breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. TNBC cells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An “Achilles cluster” of TNBC-specific genes are extremely sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in TNBC and CDK7 inhibition may be useful therapy for this challenging cancer.
2015-09-24 | GSE69106 | GEO
Project description:Basal-like breast cancer (BBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that BBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing a novel kinase inhibitor and CRISPR/Cas9-mediated gene editing, we show here that basal but not luminal breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. BBC cells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An “Achilles cluster” of BBC-specific genes are extremely sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in BBC and CDK7 inhibition may be useful therapy for this challenging cancer. ChIP-Seq for H3K27ac in basal-like breast cancer and luminal-like breast cancer cell lines
2015-01-23 | E-GEOD-65201 | biostudies-arrayexpress
Project description:Basal-like breast cancer (BBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that BBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing a novel kinase inhibitor and CRISPR/Cas9-mediated gene editing, we show here that basal but not luminal breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. BBC cells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An “Achilles cluster” of BBC-specific genes are extremely sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in BBC and CDK7 inhibition may be useful therapy for this challenging cancer.
2015-01-23 | GSE65201 | GEO
Project description:CDK7-dependent Transcriptional Addition in Basal-like Breast Cancer (ChIP-Seq)
| PRJNA273393 | ENA
Project description:Triple-negative breast cancer (TNBC) has a highly aggressive nature and distinct molecular characteristics from other subtypes of breast cancer and lacks effective targeted therapy. The molecular and genetic basis of cysteine/cystine dependency in TNBC is complex. We found that cysteine addiction associates with the expression of a set of Claudin genes in TNBC. The Claudin-high TNBCs are independent on cystine, while the Claudin-low TNBCs undergo rapid ferroptosis upon cystine deprivation or inhibition of cystine transport by erastin. To overcome the resistance of Claudin-high TNBC and luminal breast cancer to the potential targeted cystine-addiction therapy, we explored the synthetic lethality of cysteine by an epigenetic compound library screen. Several potent HDAC6 inhibitors were identified and rendered the Claudin-high TNBCs and luminal cancer cells dependent on extracellular cystine and undergoing ferroptosis upon cystine deprivation. The transcriptomic profiling showed that the HDAC6 inhibitor tubacin in combination with erastin activates a synthetic-lethal transcriptional program. Together, we have identified the HDAC6 inhibitors as potent therapy-sensitizers to revive the targeted cysteine-addiction therapy for various subtypes of breast cancer, not limit in the Claudin-low TNBC.
2021-06-02 | GSE154425 | GEO
Project description:Gene expression of triple negative breast cancer
| PRJNA1081147 | ENA