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An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis

ABSTRACT: An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis

PROVIDER: PRJNA727014 | ENA |

REPOSITORIES: ENA

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An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis

Project description:The Epithelial–Mesenchymal Transition (EMT) and primary ciliogenesis induce stem cell properties in basal Mammary Stem Cells (MaSCs) to promote mammogenesis, but the underlying mechanisms remain incompletely understood. Here, we show that EMT transcription factors promote ciliogenesis upon intermediate EMT transition states by activating ciliogenesis inducers, including FGFR1. The resulting primary cilia promote BBS11-dependent ubiquitination and inactivation of a central signaling node, GLIS2. We show that GLIS2 inactivation promotes MaSC stemness, and GLIS2 is required for normal mammary gland development. Moreover, GLIS2 inactivation is required to induce the proliferative and tumorigenic capacities of the Mammary-Tumor-initiating cells (MaTICs) of claudin-low breast cancers. Claudin-low breast tumors can be segregated from other breast tumor subtypes based on a GLIS2-dependent gene expression signature. Collectively, our findings establish molecular mechanisms by which EMT programs induce ciliogenesis to control MaSC and MaTIC biology, mammary gland development, and claudin-low breast cancer formation.

2021-10-05 | GSE173788 | GEO

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

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Project description: Not available

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Identification of EMT and EMT/Cilium-dependent gene expression signatures + Identification of breast tumors of the claudin-low molecular subtype among triple-negative breast cancers

Project description:Identification of EMT and EMT/Cilium-dependent gene expression signatures + Identification of breast tumors of the claudin-low molecular subtype among triple-negative breast cancers

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Identification of EMT and EMT/Cilium-dependent gene expression signatures + Identification of breast tumors of the claudin-low molecular subtype among triple-negative breast cancers II

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Genome-wide screen of transcription co-regulators identifies GLIS2 as a repressor for p53 target genes [ChIP-seq]

Project description:GLIS2, a member of the sub-family of Krüppel-like zinc finger proteins, has been linked to the development of nephronophthisis, while few studies have been conducted on the connection between tumorigenesis and GLIS2. In the current study, we identified GLIS2 as a repressor for p53 target genes, such as PUMA. GLIS2 ChIP-seq demonstrated that GLIS2 binds directly on PUMA promoter. In addition, GLIS2 inhibits the binding of p53 on PUMA promoter region and the modification of H3K27ac on PUMA enhancer. Taken together, GLIS2 is identified as an oncogene in colorectal cancer.

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Genome-wide screen of transcription co-regulators identifies GLIS2 as a repressor for p53 target genes [RNA-seq]

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

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.

2012-07-24 | GSE32727 | GEO

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

2012-07-24 | GSE32904 | GEO

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

2012-07-23 | E-GEOD-32904 | biostudies-arrayexpress