2020
Kahounová, Zuzana; Remšík, Ján; Fedr, Radek; Bouchal, Jan; Mičková, Alena; Slabáková, Eva; Binó, Lucia; Hampl, Aleš; Souček, Karel
Slug-expressing mouse prostate epithelial cells have increased stem cell potential. Journal Article
In: Stem cell research, vol. 46, pp. 101844, 2020, ISSN: 1876-7753 1873-5061, (Place: England).
Abstract | Links | BibTeX | Tags: *Epithelial-Mesenchymal Transition, *Prostate, Animals, Cell Line, Cell Movement, Epithelial Cells, epithelial-to-mesenchymal transition, Male, Mice, Organoids, Prostate stem cells, Snai2/Slug, Snail Family Transcription Factors/genetics, stemness, Tumor
@article{kahounova_slug-expressing_2020,
title = {Slug-expressing mouse prostate epithelial cells have increased stem cell potential.},
author = {Zuzana Kahounová and Ján Remšík and Radek Fedr and Jan Bouchal and Alena Mičková and Eva Slabáková and Lucia Binó and Aleš Hampl and Karel Souček},
doi = {10.1016/j.scr.2020.101844},
issn = {1876-7753 1873-5061},
year = {2020},
date = {2020-07-01},
journal = {Stem cell research},
volume = {46},
pages = {101844},
abstract = {Deciphering the properties of adult stem cells is crucial for understanding of their role in healthy tissue and in cancer progression as well. Both stem cells and cancer stem cells have shown association with epithelial-to-mesenchymal transition (EMT) in various tissue types. Aiming to investigate the epithelial and mesenchymal phenotypic traits in adult mouse prostate, we sorted subpopulations of basal prostate stem cells (mPSCs) and assessed the expression levels of EMT regulators and markers with custom-designed gene expression array. The population of mPSCs defined by a Lin(-)/Sca-1(+)CD49f(hi)/Trop-2(+) (LSC Trop-2(+)) surface phenotype was enriched in mesenchymal markers, especially EMT master regulator Slug, encoded by the Snai2 gene. To further dissect the role of Slug in mPSCs, we used transgenic Snai2(tm1.1Wbg) reporter mouse strain. Using this model, we confirmed the presence of mesenchymal traits and increase of organoid forming capacity in Slug(+) population of mPSCs. The Slug(+)-derived organoids comprised all prostate epithelial cell types - basal, luminal, and neuroendocrine. Collectively, these data uncover the important role of Slug expression in the physiology of mouse prostate stem cells.},
note = {Place: England},
keywords = {*Epithelial-Mesenchymal Transition, *Prostate, Animals, Cell Line, Cell Movement, Epithelial Cells, epithelial-to-mesenchymal transition, Male, Mice, Organoids, Prostate stem cells, Snai2/Slug, Snail Family Transcription Factors/genetics, stemness, Tumor},
pubstate = {published},
tppubtype = {article}
}
Deciphering the properties of adult stem cells is crucial for understanding of their role in healthy tissue and in cancer progression as well. Both stem cells and cancer stem cells have shown association with epithelial-to-mesenchymal transition (EMT) in various tissue types. Aiming to investigate the epithelial and mesenchymal phenotypic traits in adult mouse prostate, we sorted subpopulations of basal prostate stem cells (mPSCs) and assessed the expression levels of EMT regulators and markers with custom-designed gene expression array. The population of mPSCs defined by a Lin(-)/Sca-1(+)CD49f(hi)/Trop-2(+) (LSC Trop-2(+)) surface phenotype was enriched in mesenchymal markers, especially EMT master regulator Slug, encoded by the Snai2 gene. To further dissect the role of Slug in mPSCs, we used transgenic Snai2(tm1.1Wbg) reporter mouse strain. Using this model, we confirmed the presence of mesenchymal traits and increase of organoid forming capacity in Slug(+) population of mPSCs. The Slug(+)-derived organoids comprised all prostate epithelial cell types - basal, luminal, and neuroendocrine. Collectively, these data uncover the important role of Slug expression in the physiology of mouse prostate stem cells.
2011
Slabáková, Eva; Pernicová, Zuzana; Slavíčková, Eva; Staršíchová, Andrea; Kozubík, Alois; Souček, Karel
TGF-β1-induced EMT of non-transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug. Journal Article
In: The Prostate, vol. 71, no. 12, pp. 1332–1343, 2011, ISSN: 1097-0045 0270-4137, (Place: United States).
Abstract | Links | BibTeX | Tags: *Epithelial-Mesenchymal Transition/genetics, Biomarkers/metabolism, Cell Line, Cell Movement, Homeodomain Proteins/genetics, Humans, Kinetics, Male, Messenger/metabolism, MicroRNAs/metabolism, Neoplasm Invasiveness/genetics, Phenotype, Prostatic Hyperplasia/*physiopathology, Repressor Proteins/genetics, RNA, Snail Family Transcription Factors, Transcription Factors/*biosynthesis/genetics, Transforming Growth Factor beta1/*pharmacology, Up-Regulation/drug effects, Vimentin/metabolism, Zinc Finger E-box Binding Homeobox 2, Zinc Finger E-box-Binding Homeobox 1
@article{slabakova_tgf-1-induced_2011,
title = {TGF-β1-induced EMT of non-transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug.},
author = {Eva Slabáková and Zuzana Pernicová and Eva Slavíčková and Andrea Staršíchová and Alois Kozubík and Karel Souček},
doi = {10.1002/pros.21350},
issn = {1097-0045 0270-4137},
year = {2011},
date = {2011-09-01},
journal = {The Prostate},
volume = {71},
number = {12},
pages = {1332–1343},
abstract = {BACKGROUND: Epithelial-mesenchymal transition (EMT) underlying cancer cell invasion and metastasis has been thoroughly studied in prostate cancer. Although EMT markers have been clinically observed in benign prostate hyperplasia, molecular events underlying the onset and progression of EMT in benign prostate cells have not been described. METHODS: EMT in BPH-1 cells was induced by TGF-β1 treatment and the kinetics of expression of EMT markers, regulators, and selected miRNAs was assessed by western blotting and quantitative RT-PCR. RESULTS: EMT in BPH-1 cells was accompanied by rapid up-regulation of SNAI2/Slug and ZEB1 transcription factors, while changes in expression levels of ZEB2 and miR-200 family members were observed after extended time intervals. Invasive phenotype with EMT hallmarks, characterizing tumorigenic clones derived from BPH-1 cells, was associated with increased mRNA levels of SNAI2, ZEB1, and ZEB2, but was not associated with significant changes in basal levels of miR-200 family members. RNA interference revealed that SNAI2/Slug is crucial for TGF-β1-induced vimentin up-regulation and migration of BPH-1 cells. CONCLUSIONS: This study suggests that in BPH-1 cells the transcription factor SNAI2/Slug is important for EMT initiation, while the ZEB family of transcription factors in cooperation with the miR-200 family may oppose the reversal of the EMT phenotype.},
note = {Place: United States},
keywords = {*Epithelial-Mesenchymal Transition/genetics, Biomarkers/metabolism, Cell Line, Cell Movement, Homeodomain Proteins/genetics, Humans, Kinetics, Male, Messenger/metabolism, MicroRNAs/metabolism, Neoplasm Invasiveness/genetics, Phenotype, Prostatic Hyperplasia/*physiopathology, Repressor Proteins/genetics, RNA, Snail Family Transcription Factors, Transcription Factors/*biosynthesis/genetics, Transforming Growth Factor beta1/*pharmacology, Up-Regulation/drug effects, Vimentin/metabolism, Zinc Finger E-box Binding Homeobox 2, Zinc Finger E-box-Binding Homeobox 1},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Epithelial-mesenchymal transition (EMT) underlying cancer cell invasion and metastasis has been thoroughly studied in prostate cancer. Although EMT markers have been clinically observed in benign prostate hyperplasia, molecular events underlying the onset and progression of EMT in benign prostate cells have not been described. METHODS: EMT in BPH-1 cells was induced by TGF-β1 treatment and the kinetics of expression of EMT markers, regulators, and selected miRNAs was assessed by western blotting and quantitative RT-PCR. RESULTS: EMT in BPH-1 cells was accompanied by rapid up-regulation of SNAI2/Slug and ZEB1 transcription factors, while changes in expression levels of ZEB2 and miR-200 family members were observed after extended time intervals. Invasive phenotype with EMT hallmarks, characterizing tumorigenic clones derived from BPH-1 cells, was associated with increased mRNA levels of SNAI2, ZEB1, and ZEB2, but was not associated with significant changes in basal levels of miR-200 family members. RNA interference revealed that SNAI2/Slug is crucial for TGF-β1-induced vimentin up-regulation and migration of BPH-1 cells. CONCLUSIONS: This study suggests that in BPH-1 cells the transcription factor SNAI2/Slug is important for EMT initiation, while the ZEB family of transcription factors in cooperation with the miR-200 family may oppose the reversal of the EMT phenotype.