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Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer

ABSTRACT: Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer

PROVIDER: PRJNA639123 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12004629_1.fastq.gz	Fastqsanger.gz
	SRR12004629_2.fastq.gz	Fastqsanger.gz
	SRR12004630_1.fastq.gz	Fastqsanger.gz
	SRR12004630_2.fastq.gz	Fastqsanger.gz
	SRR12004631_1.fastq.gz	Fastqsanger.gz

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Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer [LATS_scRNAseq]

Project description:Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer [LATS_scRNAseq]

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Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer [Organoid_RNAseq]

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Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer [DSS_scRNAseq]

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Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer [DSS_scRNAseq]

Project description:Although the Hippo transcriptional coactivator YAP is considered oncogenic in many tissues, its roles in intestinal homeostasis and colorectal cancer (CRC) remain controversial. Here, we demonstrate that the Hippo kinases LATS1/2 and MST1/2, which inhibit YAP activity, are required for maintaining Wnt signaling and canonical stem cell function. Hippo inhibition induces a distinct epithelial cell state marked by low Wnt signaling, a wound-healing response, and transcription factor Klf6 expression. Notably, loss of LATS1/2 or overexpression of YAP is sufficient to reprogram Lgr5+ cancer stem cells to this state and thereby suppress tumor growth in organoids, patient-derived xenografts, and mouse models of primary and metastatic CRC. Finally, we demonstrate that genetic deletion of YAP and its paralog TAZ promotes the growth of these tumors. Collectively, our results establish the role of YAP as a tumor suppressor in the adult colon and implicate Hippo kinases as therapeutic vulnerabilities in colorectal malignancies.

2020-06-24 | GSE152369 | GEO

Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer [Organoid_RNAseq]

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Regenerative Reprogramming of the Intestinal Stem Cell State via Hippo Signaling Suppresses Metastatic Colorectal Cancer.

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Regenerative reprogramming of the intestinal stem cell state via Hippo signaling suppresses metastatic colorectal cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-06-24 | GSE152376 | GEO

PAX3-FOXO1 suppresses cellular senescence through RASSF4-mediated restraint of the mammalian Hippo/MST1 pathway

Project description:Alveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression of the PAX3-FOXO1 fusion gene. Despite its discovery over almost 20 years ago, PAX3-FOXO1 remains an enigmatic tumor driver. Previously, we reported that PAX3-FOXO1 supports aRMS initiation by enabling bypass of cellular senescence. Here, we show that bypass occurs in part by PAX3-FOXO1-mediated upregulation of RASSF4, a Ras-association domain family (RASSF) member, which then suppresses the evolutionarily conserved mammalian Hippo/Mst1 pathway. RASSF4 loss-of-function activates Hippo/Mst1 and inhibits downstream YAP, causing aRMS cell cycle arrest and senescence. This is the first evidence for an oncogenic role for RASSF4, and a novel mechanism for Hippo signaling suppression in human cancer. Human skeletal muscle myoblasts (HSMMs) were retrovirally transduced with either an empty vector (Vp, pK1) or PAX3-FOXO1 (PFp, pK1-PAX3-FOXO1) and selected on puromycin. Presenescent (presen) cells were harvested before the senescence checkpoint. Since cells expressing PAX3-FOXO1 can bypass the senescence checkpoint, postsenescent (postsen) cells expressing PAX3-FOXO1 were also harvested. the gene expression affected by the introduction of PAX3-FOXO1

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DUB1 suppresses Hippo signaling via modulating TAZ protein in gastric cancer

Project description:DUB1 suppresses Hippo signaling via modulating TAZ protein in gastric cancer

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