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Sphingomyelins secreted by mammosphere-derived cells present a novel mechanism for the low mammary cancer incidence observed in certain mammals

ABSTRACT: Sphingomyelins secreted by mammosphere-derived cells present a novel mechanism for the low mammary cancer incidence observed in certain mammals

PROVIDER: PRJNA607524 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11112577.fastq.gz	Fastqsanger.gz
	SRR11112578.fastq.gz	Fastqsanger.gz
	SRR11112579.fastq.gz	Fastqsanger.gz
	SRR11112580.fastq.gz	Fastqsanger.gz
	SRR11112581.fastq.gz	Fastqsanger.gz

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Sphingomyelins secreted by mammosphere-derived cells present a novel mechanism for the low mammary cancer incidence observed in certain mammals

Project description:We describe a novel mechanism by which mammals with a low mamary cancer incidence may avert mammary cancer development.

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Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals.

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Project description:Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is silenced by promoter methylation in many types of tumors, yet ASC’s role in most cancers remains unknown. Here, we show that ASC is highly expressed in a model of medulloblastoma, the most common malignant pediatric brain cancer. Importantly, while ASC deficiency did not affect normal cerebellar development, ASC knock-out mice in the Smoothened (ND2:SmoA1) transgenic model of medulloblastoma exhibited a profound reduction in medulloblastoma incidence and delayed tumor onset. Premalignant lesions in cerebella of ASC-/-;ND2:SmoA1 mice displayed a striking decrease in number of ectopic progenitors. While proliferation rates decreased with ASC deletion, apoptosis and differentiation markers remained unchanged. Interestingly, ASC deficiency disrupted expression of genes in the TGF-ß pathway and increased the level of nuclear Smad3 in this medulloblastoma model. Together, these results demonstrate an unexpected requirement for ASC in Sonic hedgehog-driven medulloblastoma tumorigenesis, thus identifying ASC as a promising novel target for anti-tumor therapy. reference x sample

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