Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA256186 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Malignant carcinomas that recur following therapy are typically de-differentiated and multi-drug resistant (MDR). De-differentiated cancer cells acquire MDR by upregulating reactive oxygen species (ROS)-scavenging enzymes and drug efflux pumps, but how these genes are upregulated in response to de-differentiation is not known. Here, we examine this question by using global transcriptional profiling to identify ROS-induced genes that are already upregulated in de-differentiated cells, even in the absence of oxidative damage. Using this approach, we found that the Nrf2 transcription factor, which is the master regulator of cellular response to oxidative stress, is pre-activated in de-differentiated cells. In de-differentiated cells, Nrf2 is not activated by oxidation but rather through a non-canonical mechanism involving its phosphorylation by the ER membrane kinase PERK. In contrast, differentiated cells require oxidative damage to activate Nrf2. Constitutive PERK-Nrf2 signaling protects de-differentiated cells from chemotherapy by reducing ROS levels and increasing drug efflux. These findings are validated in therapy-resistant basal breast cancer cell lines and animal models, where inhibition of the PERK-Nrf2 signaling axis reversed the MDR of de-differentiated cancer cells. Additionally, analysis of patient tumor datasets showed that a PERK pathway signature correlates strongly with chemotherapy resistance, tumor grade, and overall survival. Collectively, these results indicate that de-differentiated cells upregulate MDR genes via PERK-Nrf2 signaling, and suggest that targeting this pathway could sensitize drug-resistant cells to chemotherapy. Differentiated human breast epithelial cells (HMLE-shGFP) or de-differentiated cells (HMLE-Twist) were treated in culture with 40uM menadione for 2 hours or 1uM PERK inhibitor for 48 hours and compared to control DMSO-treated cells.
2014-10-01 | E-GEOD-59780 | biostudies-arrayexpress
Project description:We quantified protein expression changes between epithelial and mesechymal stages in immortalized human mammary epithelial cells (HMLE). Epithelial–mesenchymal transition is induced by expressing an EMT-TF, Twist.
2019-06-24 | PXD012001 | Pride
Project description:Twist is a key EMT inducer, expression of Twist will induce EMT in HMLE and breast tumor T47D cells By expressing Twist in HMLE and T47D cells, which lack the expression of Twist, will identify the genes regulated by Twist Expressing Twist in HMLE and T47D cells, stable clones were selected and treated with BET inhibitor JQ1 and RNA were prepared for microarray analysis
2013-12-12 | E-GEOD-53222 | biostudies-arrayexpress
Project description:RNA-seq of two human mammary epithelial cell lines (HMLE and HMLE-Twist-ER) treated with 4-hydroxytamoxifen vs control
| PRJEB39425 | ENA
Project description:Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial-mesenchymal transitions (EMTs) occurring in wound healing processes and the cancer stem cell-like compartment of tumors, including TGF-β-dependence, we investigated the role of a Grainyhead gene (GRHL2) in oncogenic EMT. Grainyhead was specifically down-regulated in the claudin-low subclass of mammary tumors and in the basal-B subclass of breast cancer cell lines. Functionally, GRHL2 suppressed TGF-β-induced, Twist-induced or spontaneous EMT, enhanced anoikis-sensitivity, and suppressed mammosphere generation in mammary epithelial cells. These effects were mediated, in part, by its suppression of ZEB1 expression, through direct repression of the ZEB1 promoter. GRHL2 also inhibited Smad-mediated transcription, and up-regulated mir200b/c as well as the TGF-β receptor antagonist, BMP2. The expression of GRHL2 in the breast cancer cell line MDA-MB-231 triggered a mesenchymal-to-epithelial transition and sensitized the cells to anoikis. These results indicate that GRHL2 is a suppressor of the oncogenic EMT. 3 biologic replicates for each cell line. Comparison of HMLE+Twist-ER cells expressing GRHL2/pMIG vs. HMLE+Twist-ER cells expressing empty pMIG.
2012-02-25 | E-GEOD-36081 | biostudies-arrayexpress
Project description:Twist is a key EMT inducer, expression of Twist will induce EMT in HMLE and breast tumor T47D cells By expressing Twist in HMLE and T47D cells, which lack the expression of Twist, will identify the genes regulated by Twist
2013-12-12 | GSE53222 | GEO
Project description:The EMT program allows epithelial cells to become endowed with motility, invasiveness and stem cell traits. We investigated difference in signaling networks that are differentially utilized in EMTed and non-EMTed cells, thereby identifying therapeutic targets that are unique to EMT/cancer stem cells. We expressed the EMT transcription factors, Twist, Snail and Slug in HMLE human mammary epithelial cells, and compared their gene expression with parental cells. We identified kinases that are more differentially regulated between the epithelial and mesenchymal cell state.
2013-09-09 | E-GEOD-43495 | biostudies-arrayexpress
Project description:We find that in invasive HMLE-Twist-ER cells, SMARCE1 binds to ILF3 and is localized to ILF motifs. In contrast, ILF motifs were not enriched at SMARCE1-bound sites in noninvasive HMLE-Twist-ER cells or at SMARCC1-bound sites.
2017-03-23 | GSE96933 | GEO
Project description:Epithelial-to-mesenchymal transition (EMT) gives rise to cells with properties similar to cancer stem cells (CSCs) that drive tumor metastasis. Recently, a screening of a large compound library on a breast EMT model has identified salinomycin, a K+/H+ ionophore, as a highly selective drug towards CSCs. We used the same EMT model to show that salinomycin targets Golgi apparatus. We have performed RNA-seq analysis on HMLE-Twist and HMLE-pBp cells (EMT and non-EMT) that were either mock treated or treated for 24h with micro molar concentration (0.2uM) of salinomycin. Salinomycin induced expression of genes enriched by known ER and Golgi stressors.
2023-01-11 | GSE124975 | GEO
Project description:Snail and Twist are two EMT inducer, expression of Snail or Twist will induce EMT in HMLE and MCF10A cells. By introducing Snail or Twist in HMLE and MCF10A cells, which lack the expression of these two proteins, will identify the genes are induced during EMT. We used microarray analysis to compare the gene expression profiles between the mammamry epithleial cells and the cells undergone EMT.
2020-01-10 | GSE143349 | GEO