Latest Publications

@article{lenart_trop2_2020,

title = {Trop2: Jack of All Trades, Master of None.},

author = {Sára Lenárt and Peter Lenárt and Jan Šmarda and Ján Remšík and Karel Souček and Petr Beneš},

doi = {10.3390/cancers12113328},

issn = {2072-6694},

year  = {2020},

date = {2020-11-01},

journal = {Cancers},

volume = {12},

number = {11},

abstract = {Trophoblast cell surface antigen 2 (Trop2) is a widely expressed glycoprotein and an epithelial cell adhesion molecule (EpCAM) family member. Although initially identified as a transmembrane protein, other subcellular localizations and processed forms were described. Its congenital mutations cause a gelatinous drop-like corneal dystrophy, a disease characterized by loss of barrier function in corneal epithelial cells. Trop2 is considered a stem cell marker and its expression associates with regenerative capacity in various tissues. Trop2 overexpression was described in tumors of different origins; however, functional studies revealed both oncogenic and tumor suppressor roles. Nevertheless, therapeutic potential of Trop2 was recognized and clinical studies with drug-antibody conjugates have been initiated in various cancer types. One of these agents, sacituzumab govitecan, has been recently granted an accelerated approval for therapy of metastatic triple-negative breast cancer. In this article, we review the current knowledge about the yet controversial function of Trop2 in homeostasis and pathology.},

note = {Place: Switzerland},

keywords = {cancer, epithelial-to-mesenchymal transition, metastases, proliferation, TACSTD2, therapy, Trop2},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{kahounova_fibroblast_2018,

title = {The fibroblast surface markers FAP, anti-fibroblast, and FSP are expressed by cells of epithelial origin and may be altered during epithelial-to-mesenchymal transition.},

author = {Zuzana Kahounová and Daniela Kurfürstová and Jan Bouchal and Gvantsa Kharaishvili and Jiří Navrátil and Ján Remšík and Šárka Šimečková and Vladimír Študent and Alois Kozubík and Karel Souček},

doi = {10.1002/cyto.a.23101},

issn = {1552-4930 1552-4922},

year  = {2018},

date = {2018-07-01},

journal = {Cytometry. Part A : the journal of the International Society for Analytical Cytology},

volume = {93},

number = {9},

pages = {941–951},

abstract = {The identification of fibroblasts and cancer-associated fibroblasts from human cancer tissue using surface markers is difficult, especially because the markers used currently are usually not expressed solely by fibroblasts, and the identification of fibroblast-specific surface molecules is still under investigation. It was aimed to compare three commercially available antibodies in the detection of different surface epitopes of fibroblasts (anti-fibroblast, fibroblast activation protein α, and fibroblast surface protein). The specificity of their expression, employing fibroblast cell lines and tumor-derived fibroblasts from breast and prostate tissues was investigated. Both the established fibroblast cell line HFF-1 and ex vivo primary fibroblasts isolated from breast and prostate cancer tissues expressed the tested surface markers to different degrees. Surprisingly, those markers were expressed also by permanent cell lines of epithelial origin, both benign and cancer-derived (breast-cell lines MCF 10A, HMLE and prostate-cell lines BPH-1, DU 145, and PC-3). The expression of fibroblast activation protein α increased on the surface of previously described models of epithelial cells undergoing epithelial-to-mesenchymal transition in response to treatment with TGF-β1. To prove the co-expression of the fibroblast markers on cells of epithelial origin, we used freshly dissociated human prostate and breast cancer tissues. The results confirmed the co-expression of anti-fibroblast and fibroblast surface protein on CD31/CD45-negative/EpCAM-positive epithelial cells. In summary, our data support the findings that the tested fibroblast markers are not fibroblast specific and may be expressed also by cells of epithelial origin (e.g., cells undergoing EMT). Therefore, the expression of these markers should be interpreted with caution, and the combination of several epitopes for both positive (anti-fibroblast or fibroblast activation protein α) and negative (EpCAM) identification of fibroblasts from breast and prostate tumor tissues is advised. © 2017 International Society for Advancement of Cytometry.},

note = {Place: United States},

keywords = {anti-fibroblast, Biomarkers/*metabolism, Breast Neoplasms/metabolism, cancer-associated fibroblasts, Cell Line, Endopeptidases, Epithelial Cell Adhesion Molecule/metabolism, Epithelial Cells/metabolism, Epithelial-Mesenchymal Transition/*physiology, epithelial-to-mesenchymal transition, Female, fibroblast activation protein α, fibroblast surface protein, Fibroblasts/*metabolism, Gelatinases/*metabolism, Humans, Leukocyte Common Antigens/metabolism, Male, Membrane Proteins/*metabolism, PC-3 Cells, Platelet Endothelial Cell Adhesion Molecule-1/metabolism, Prostatic Neoplasms/metabolism, Serine Endopeptidases/*metabolism, Transforming Growth Factor beta1/metabolism, Tumor},

pubstate = {published},

tppubtype = {article}

}

@article{kratochvilova_tumor_2015,

title = {Tumor suppressor candidate 3 (TUSC3) prevents the epithelial-to-mesenchymal transition and inhibits tumor growth by modulating the endoplasmic reticulum stress response in ovarian cancer cells.},

author = {Kateřina Kratochvílová and Peter Horak and Milan Ešner and Karel Souček and Dietmar Pils and Mariam Anees and Erwin Tomasich and František Dráfi and Veronika Jurtíková and Aleš Hampl and Michael Krainer and Petr Vaňhara},

doi = {10.1002/ijc.29502},

issn = {1097-0215 0020-7136},

year  = {2015},

date = {2015-09-01},

journal = {International journal of cancer},

volume = {137},

number = {6},

pages = {1330–1340},

abstract = {Ovarian cancer is one of the most common malignancies in women and contributes greatly to cancer-related deaths. Tumor suppressor candidate 3 (TUSC3) is a putative tumor suppressor gene located at chromosomal region 8p22, which is often lost in epithelial cancers. Epigenetic silencing of TUSC3 has been associated with poor prognosis, and hypermethylation of its promoter provides an independent biomarker of overall and disease-free survival in ovarian cancer patients. TUSC3 is localized to the endoplasmic reticulum in an oligosaccharyl tranferase complex responsible for the N-glycosylation of proteins. However, the precise molecular role of TUSC3 in ovarian cancer remains unclear. In this study, we establish TUSC3 as a novel ovarian cancer tumor suppressor using a xenograft mouse model and demonstrate that loss of TUSC3 alters the molecular response to endoplasmic reticulum stress and induces hallmarks of the epithelial-to-mesenchymal transition in ovarian cancer cells. In summary, we have confirmed the tumor-suppressive function of TUSC3 and identified the possible mechanism driving TUSC3-deficient ovarian cancer cells toward a malignant phenotype.},

note = {Place: United States},

keywords = {Animals, Cell Line, Endoplasmic Reticulum Stress, Endoplasmic Reticulum Stress/*genetics, Epithelial-Mesenchymal Transition/*genetics, epithelial-to-mesenchymal transition, Female, Genes, Heterografts, Humans, Inbred NOD, Membrane Proteins/*genetics, Mice, N33, ovarian cancer, Ovarian Neoplasms/*genetics, SCID, Tumor, Tumor Suppressor, Tumor Suppressor Proteins/*genetics, Tumor Suppressor/physiology, TUSC3},

pubstate = {published},

tppubtype = {article}

}