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Epigenetic rewiring towards mesenchymal-epithelial transformation in ovarian cancer-associated mesenchymal stem cells drives metastasis

ABSTRACT: Epigenetic rewiring towards mesenchymal-epithelial transformation in ovarian cancer-associated mesenchymal stem cells drives metastasis

PROVIDER: PRJNA574449 | ENA |

REPOSITORIES: ENA

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Epigenetic rewiring towards mesenchymal-epithelial transformation in ovarian cancer-associated mesenchymal stem cells drives metastasis

Project description:Ovarian cancer develops early intra-peritoneal metastasis establishing a pro-tumorigenic tumor microenvironment (TME) through reprogramming normal mesenchymal stem cells into carcinoma-associated mesenchymal stem cells (CA-MSCs). CA-MSCs are the stromal stem cell of the TME, supporting cancer growth, increasing desmoplasia, angiogenesis and chemotherapy resistance. We demonstrate epigenetic rewiring drives CA-MSC formation via enhancer-enriched DNA hypermethylation, altered chromatin accessibility and differential histone modifications inducing a partial mesenchymal to epithelial transition (MET) increasing tumor cell adhesion. Direct CA-MSC:tumor cell interactions, confirmed in patient ascites, facilitate ovarian cancer metastasis through co-migration. WT1, a developmental mediator of MET, and EZH2, mediate CA-MSC epigenetic reprogramming. WT1 overexpression induces CA-MSC conversion while WT1 knock-down, in combination with EZH2 inhibition, blocks CA-MSC formation. EZH2 inhibition subsequently decreases intra-abdominal metastasis.

2020-12-22 | GSE138072 | GEO

Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation

Project description:Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation

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EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors

Project description:This SuperSeries is composed of the following subset Series: GSE32727: EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [human] GSE32904: EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [mouse] Refer to individual Series

2012-07-23 | E-GEOD-32905 | biostudies-arrayexpress

Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation

Project description:Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation

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Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation

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Loss of ∆Np63 induces epigenetic rewiring and enhances plasticity towards alveolar identity

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Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation [II]

Project description:Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation [II]

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Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation [I]

Project description:Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation [I]

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EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [mouse]

Project description:The newly identified claudin-low subtype of cancer is believed to represent the most primitive breast malignancies, having arisen from transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this hypothesis, we show both in vitro and in vivo that transcription factors inducing epithelial-mesenchymal transition can drive the development of claudin-low tumors from differentiated mammary epithelial cells, by playing a dual role in cell transformation and dedifferentiation.

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