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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 28, 2024 |
| Title |
SMARCA4 controls state plasticity in small cell lung cancer through regulation of neuroendocrine transcription factors and REST splicing [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Small Cell Lung Cancer (SCLC) can be classified into transcriptional subtypes with distinct degrees of neuroendocrine (NE) differentiation. Recent evidence supports plasticity among subtypes with a bias toward adoption of low-NE states during disease progression or upon acquired chemotherapy resistance. Here, we identify a role for SMARCA4, the catalytic subunit of the SWI/SNF complex, as a regulator of subtype shift in SCLC. SMARCA4 binds to gene loci encoding NE-lineage transcription factors ASCL1 and NEUROD1 and alters chromatin accessibility, suppressing NE programs. In parallel, SMARCA4 also controls REST, a known suppressor of the NE phenotype, by regulating SRRM4-dependent REST splicing. The SMARCA2/4 inhibitor FHD-286 induces loss of NE features and drives ERBB pathway activation in SCLC, rendering SCLC tumors sensitive to afatinib. This study nominates SMARCA4 as a key regulator of the NE state plasticity and defines a novel therapeutic strategy for SCLC.
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| Overall design |
SMARCA4 ChipSeq in 4 neuroendocrine SCLC PDXs
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| Contributor(s) |
Redin E, Zhan YA, Rudin CM |
| Citation(s) |
39080761 |
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| Submission date |
Feb 22, 2024 |
| Last update date |
Aug 29, 2024 |
| Contact name |
Yingqian Ada Zhan |
| E-mail(s) |
zhany@mskcc.org
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| Organization name |
MSKCC
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| Department |
EPIGENETICS RESEARCH CENTER
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| Street address |
430 East 67th Street
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| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA1079238 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE256346_RAW.tar |
1.2 Gb |
(http)(custom) |
TAR (of BW, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
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