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The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors (ATAC-Seq)

ABSTRACT: The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors (ATAC-Seq)

PROVIDER: PRJNA1149013 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30275165_1.fastq.gz	Fastqsanger.gz
	SRR30275165_2.fastq.gz	Fastqsanger.gz
	SRR30275166_1.fastq.gz	Fastqsanger.gz
	SRR30275166_2.fastq.gz	Fastqsanger.gz
	SRR30275167_1.fastq.gz	Fastqsanger.gz

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The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors

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The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors (RNA-Seq)

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The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors (ATAC-Seq)

Project description:Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive sarcoma that may be seen in patients with neurofibromatosis type 1 (NF1) or occur sporadically. While surgery is the primary treatment for localized MPNST with a 61.9% overall survival rate, metastatic disease is often fatal due to resistance to systemic therapies which underscores the urgent need for effective treatments. MPNSTs frequently harbor inactivating driver mutations in the PRC2 epigenetic repressor complex suggesting epigenetic therapies may represent a specific vulnerability in these tumors. Here, we investigate the role of the LSD1-HDAC1-CoREST (LHC) repressor complex in mediating MPNST tumor growth and progression. Our findings demonstrate that the LHC small molecule inhibitor, corin, induces apoptosis and significantly inhibits proliferation in MPNST cells. Transcriptomic analysis of corin-treated MPNST cells demonstrates specific increases in genes associated with axonogenesis and neuronal differentiation as well as altered extracellular matrix; additionally, corin treatment is shown to inhibit MPNST invasion in vitro. These results underscore the critical role of the LHC complex in facilitating MPNST growth and progression and suggest that targeting the LHC complex represents a promising therapeutic approach for this aggressive malignancy.

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Malignant peripheral nerve sheath tumor (MPNST) tumor samples

Project description:Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma. Comprehensive proteomic profiles of 23 MPNST tumor specimens were obtained using LC-MS/MS. Among 23 tumor specimens, 13 patients showed favorable prognosis and 10 did local recurrence/distant metastasis.

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Targeting RABL6A-RB1 signaling suppresses malignant peripheral nerve sheath tumors

Project description:Malignant peripheral nerve sheath tumors (MPNSTs) are deadly sarcomas that lack effective therapies. In most MPNSTs, the retinoblastoma (RB1) tumor suppressor is disabled by hyperactivation of cyclin dependent kinases (CDKs), commonly through loss of CDK inhibitory proteins such as p27(Kip1). RABL6A is an inhibitor of RB1 whose role in MPNSTs is unknown. To gain insight into MPNST development and establish new treatment options, we investigated RABL6A-RB1 signaling and CDK inhibitor-based therapy in MPNSTs.

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