Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA154399 | ENA |
REPOSITORIES: ENA
Similar Datasets
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
Project description:EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [human]
| PRJNA154383 | ENA
Project description:The distinct frequency of activation of the RAS/MAPK signaling pathway in human cancers suggests a context-dependent cellular state of vulnerability to RAS transformation. While uncommon in breast cancers, oncogenic activation of this pathway is frequent in claudin-low (CL) tumors, a subtype of breast malignancies enriched in features of epithelial-mesenchymal transition (EMT), suggesting an interplay between RAS activation and EMT. Using inducible models of human mammary epithelial cells, we show that RAS-mediated transformation relies upon cellular reprogramming governed by the EMT-inducing transcription factor ZEB1. The path to ZEB1 induction involves a paracrine process: cells entering a senescent state following RAS induction release proinflammatory cytokines, notably IL-6 and IL1 which promote ZEB1 expression and activity in neighboring cells, thereby fostering their malignant transformation. Collectively, our findings unveil a previously unprecedented role for senescence in bridging RAS activation and EMT over the course of malignant transformation of human mammary epithelial cells.
2024-02-16 | GSE201536 | GEO
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
Project description:The epithelial-mesenchymal transition (EMT) is an embryonic transdifferentiation program which consists of the conversion of polarized epithelial cells into a motile mesenchymal phenotype. EMT is aberrantly reactivated during tumor progression, promoting metastatic dissemination. Herein, we demonstrate that EMT-permissive conditions also favor tumor initiation by minimizing the number of events required for neoplastic transformation. We further demonstrated that even the partial commitment of human mammary epithelial cells into an EMT program is sufficient to confer malignant properties, suggesting that the reactivation of embryonic EMT inducers participates to the primary tumor growth long before the initiation of the invasion-metastasis cascade.
2011-01-11 | GSE26534 | GEO
Project description:The epithelial-mesenchymal transition (EMT) is an embryonic transdiffrentiation program which consists of the conversion of polarized epithelial cells into a motile mesenchymal phenotype. EMT is aberrantly reactivated during tumor progression, promoting metastatic dissemination. Herein, we demonstrate that EMT permissive conditions also favor tumor initiation by minimizing the number of events required for neoplastic transformation. We further demonstrated that even partial commitment of human mammary epithelial cells into an EMT program is sufficient to confer malignant properties, suggesting that the reactivation of embryonic EMT inducers participate to the primary tumor growth long before the initiation of the invasion-metastasis cascade.
2012-01-31 | GSE26541 | GEO
Project description:The epithelial-mesenchymal transition (EMT) is an embryonic transdiffrentiation program which consists of the conversion of polarized epithelial cells into a motile mesenchymal phenotype. EMT is aberrantly reactivated during tumor progression, promoting metastatic dissemination. Herein, we demonstrate that EMT permissive conditions also favor tumor initiation by minimizing the number of events required for neoplastic transformation. We further demonstrated that even partial commitment of human mammary epithelial cells into an EMT program is sufficient to confer malignant properties, suggesting that the reactivation of embryonic EMT inducers participate to the primary tumor growth long before the initiation of the invasion-metastasis cascade. Human mammary epithelial cells (HMEC) were sequentially depleted in p53 through RNA interference (shp53), transduced with H-RasG12V and immortalized by hTert. Two different Tert/shp53/Ras cell population emerge that display either an epithelial (Epi) or a mesenchymal (Mes) phenotype. Gene expression profiles of the Tert/shp53 control cells and of tert/shp53/Ras/Epi and Tert/shp53/Ras/Mes were analyzed.
2012-01-31 | E-GEOD-26541 | biostudies-arrayexpress
Project description:The epithelial-mesenchymal transition (EMT) is an embryonic transdifferentiation program which consists of the conversion of polarized epithelial cells into a motile mesenchymal phenotype. EMT is aberrantly reactivated during tumor progression, promoting metastatic dissemination. Herein, we demonstrate that EMT-permissive conditions also favor tumor initiation by minimizing the number of events required for neoplastic transformation. We further demonstrated that even the partial commitment of human mammary epithelial cells into an EMT program is sufficient to confer malignant properties, suggesting that the reactivation of embryonic EMT inducers participates to the primary tumor growth long before the initiation of the invasion-metastasis cascade. arrayCGH profiles analysis of Tert/shp53/Ras epithelial HMEC derivatives and 3 different tumors generated after injection of mesenchymal Tert/shp53/Ras/ HMEC derivatives in fad pads of nude mice
2011-01-11 | E-GEOD-26534 | biostudies-arrayexpress
Project description:The claudin-low subtype is a recently identified rare molecular subtype of human breast cancer that expresses low levels of tight and adherens junction genes and shows high expression of epithelial-to-mesenchymal transition (EMT) genes. These tumors are enriched in gene expression signatures derived from human tumor initiating cells (TIC) and human mammary stem cells. Through cross-species analysis, we discovered mouse mammary tumors that have similar gene expression characteristics as human claudin-low tumors and were also enriched for the human TIC signature. Such claudin-low tumors were similarly rare, but came from a number of distinct mouse models including the p53 null transplant model. Here we present a molecular characterization of fifty p53 null mammary tumors as compared to other mouse models and human breast tumor subtypes. Similar to human tumors, the murine p53 null tumors fell into multiple molecular subtypes including two basal-like, a luminal, a claudin-low, and a subtype unique to this model. The claudin-low tumors also showed high gene expression of EMT inducers, low expression of the miR-200 family, and low to absent expression of both claudin 3 and E-cadherin. These murine subtypes also contained distinct genomic DNA copy number changes some of which are similarly altered in their cognate human subtype counterpart. Finally, limiting dilution transplantation revealed that p53 null claudin-low tumors are highly enriched for TICs as compared to the more common adenocarcinomas arising in the same model, thus providing a novel preclinical mouse model to investigate the therapeutic response of TICs. 107 Agilent CGH and expression microarrays
2011-08-14 | E-GEOD-27101 | biostudies-arrayexpress