Docetaxel inhibits epithelial-mesenchymal transition in human mammary cells
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ABSTRACT:
PROVIDER: PRJNA1035779 | ENA |
REPOSITORIES: ENA
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Project description:Epithelial–mesenchymal transition (EMT) is a reversible and dynamic biological process in which epithelial cells acquire mesenchymal characteristics including enhanced stemness and migratory ability. EMT can facilitate cancer metastasis and is a known driver of cellular resistance to common chemotherapeutic drugs such as docetaxel. Current chemotherapeutic practices such as docetaxel treatment can promote EMT and increase the chance of tumour recurrence and resistance, calling for new approaches in cancer treatment. Here we show that prolonged docetaxel treatment at a sub-IC50 concentration inhibits EMT in immortalized human mammary epithelial (HMLE) cells. Using immunofluorescence, flow cytometry, and bulk transcriptomic sequencing to assess EMT progression, we analysed a range of cellular markers of EMT in docetaxel-treated cells and observed an upregulation of epithelial markers and downregulation of mesenchymal markers in the presence of docetaxel. This finding suggests that docetaxel may have clinical applications not only as a cytotoxic drug but also as an inhibitor of EMT-driven metastasis and multidrug resistance, depending on the concentration of its use.
2023-11-05 | GSE247028 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE29435: Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer: cell line data GSE29436: Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer: patient data Refer to individual Series
2012-01-26 | E-GEOD-29437 | biostudies-arrayexpress
Project description:Metronomic administration of topotecan alone and in combination with docetaxel inhibits epithelial-mesenchymal transition in aggressive variant prostate cancers
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Project description:Elf5 (or ESE-2) is an ETS transcription factor that is abundantly expressed in the mammary epithelium, where it plays a critical role in dictating cell fate and lineage choices. These changes are in part mediated by alterations in the expression and activity of critical components of the Jak/Stat pathway. While the biological function of Elf5 in mammary gland development has been well characterized, its role in breast cancer remains to be elucidated. Here we show that loss of Elf5 leads to features associated with epithelial-mesenchymal transition (EMT) in the mouse mammary gland during pregnancy and lactation. These cellular changes in Elf5-null mammary epithelia are also reflected at the molecular level by the global enrichment of EMT-related gene signatures. ELF5 is expressed in higher level in weakly metastatic breast cancer cells that retained epithelial features compared to highly metastatic cells with mesenchymal features. ELF5 knockdown in T47D breast cancer cells resulted in EMT and increased migration. Conversely, ectopic expression of Elf5 revert mesenchymal-like MDA-MB-231 cells and its lung-tropic variant LM2 to an epithelial phenotype, with reduced migration, invasion and lung metastatic abilities. Finally, we showed that Elf5 binds directly to the promoter of the EMT transcriptional factor Snail2 (Slug) and repress its expression. Taken together, these data established a novel function for Elf5 in inhibiting EMT in normal mammary epithelium and in breast cancer through direct targeting of Snail2. This SuperSeries is composed of the following subset Series: GSE32143: LM2 cell: infected with lentivirus to stably express Elf5 vs GFP GSE32144: MDA-MB-231 cell: infected with lentivirus to stably express mut-Elf5 vs WT-Elf5
2012-09-20 | E-GEOD-32150 | biostudies-arrayexpress
Project description:Digitoxin Inhibits Epithelial-to-Mesenchymal-Transition in Hereditary Castration Resistant Prostate Cancer
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Project description:Effects of Smad3 and Smad2 knock-down on TGFbeta-induced epithelial-to-mesenchymal transition (EMT) in mouse mammary epithelial (Nme) cells
2009-04-01 | E-MEXP-1342 | biostudies-arrayexpress
Project description:Every year more than 42,000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs) as well as progesterone receptor (PR) positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT). Paraffin sections from patients with (n=9) or without (n=10) progressive endometrial cancer (recurrent or metastatic disease) were assessed for the presence of CD4+ (helper), CD8+ (cytotoxic) and Foxp3+ (regulatory) T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunosurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4 and WIF1, quantitive RT-PCR was performed to verify down regulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK) endometrial cancer cell lines stably transfected with PRA (IKPRA), PRB (IKPRB) and PRA+PRB (IKPRAB) were cultured in the presence/absence of progesterone (MPA) and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT makers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA-regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-β and Wnt/β-catenin signalling. Intact progesterone signaling in non-progressive endometrial cancer seems to be an important factor stimulating immunosurveillance and inhibiting transition from an epithelial to a more mesenchymal, more invasive phenotype. From 4 non-progressive and 4 progressive patients, snap-frozen endometrial cancer tumor specimens were used for microarray analysis. Gene expression data of progressive disease was compared with non-progressive disease.
2012-01-26 | E-GEOD-29436 | biostudies-arrayexpress
Project description:Elf5 (or ESE-2) is an ETS transcription factor that is abundantly expressed in the mammary epithelium, where it plays a critical role in dictating cell fate and lineage choices. These changes are in part mediated by alterations in the expression and activity of critical components of the Jak/Stat pathway. While the biological function of Elf5 in mammary gland development has been well characterized, its role in breast cancer remains to be elucidated. Here we show that loss of Elf5 leads to features associated with epithelial-mesenchymal transition (EMT) in the mouse mammary gland during pregnancy and lactation. These cellular changes in Elf5-null mammary epithelia are also reflected at the molecular level by the global enrichment of EMT-related gene signatures. ELF5 is expressed in higher level in weakly metastatic breast cancer cells that retained epithelial features compared to highly metastatic cells with mesenchymal features. ELF5 knockdown in T47D breast cancer cells resulted in EMT and increased migration. Conversely, ectopic expression of Elf5 revert mesenchymal-like MDA-MB-231 cells and its lung-tropic variant LM2 to an epithelial phenotype, with reduced migration, invasion and lung metastatic abilities. Finally, we showed that Elf5 binds directly to the promoter of the EMT transcriptional factor Snail2 (Slug) and repress its expression. Taken together, these data established a novel function for Elf5 in inhibiting EMT in normal mammary epithelium and in breast cancer through direct targeting of Snail2. This SuperSeries is composed of the SubSeries listed below.
2012-09-20 | GSE32150 | GEO
Project description:Oleanolic acid inhibits epithelial–mesenchymal transition of hepatocellular carcinoma by promoting iNOS dimerization
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