Latest Publications

@article{karasova_inhibition_2022,

title = {Inhibition of Aryl Hydrocarbon Receptor (AhR) Expression Disrupts Cell Proliferation and Alters Energy Metabolism and Fatty Acid Synthesis in Colon Cancer Cells.},

author = {Martina Karasová and Jiřina Procházková and Zuzana Tylichová and Radek Fedr and Miroslav Ciganek and Miroslav Machala and Zdeněk Dvořák and Barbora Vyhlídalová and Iveta Zůvalová and Jiří Ehrmann and Jan Bouchal and Zdeněk Andrysík and Jan Vondráček},

doi = {10.3390/cancers14174245},

issn = {2072-6694},

year  = {2022},

date = {2022-08-01},

journal = {Cancers},

volume = {14},

number = {17},

abstract = {The aryl hydrocarbon receptor (AhR) plays a wide range of physiological roles in cellular processes such as proliferation, migration or control of immune responses. Several studies have also indicated that AhR might contribute to the regulation of energy balance or cellular metabolism. We observed that the AhR is upregulated in tumor epithelial cells derived from colon cancer patients. Using wild-type and the corresponding AhR knockout (AhR KO) variants of human colon cancer cell lines HCT116 and HT-29, we analyzed possible role(s) of the AhR in cell proliferation and metabolism, with a focus on regulation of the synthesis of fatty acids (FAs). We observed a decreased proliferation rate in the AhR KO cells, which was accompanied with altered cell cycle progression, as well as a decreased ATP production. We also found reduced mRNA levels of key enzymes of the FA biosynthetic pathway in AhR KO colon cancer cells, in particular of stearoyl-CoA desaturase 1 (SCD1). The loss of AhR was also associated with reduced expression and/or activity of components of the PI3K/Akt pathway, which controls lipid metabolism, and other lipogenic transcriptional regulators, such as sterol regulatory element binding transcription factor 1 (SREBP1). Together, our data indicate that disruption of AhR activity in colon tumor cells may, likely in a cell-specific manner, limit their proliferation, which could be linked with a suppressive effect on their endogenous FA metabolism. More attention should be paid to potential mechanistic links between overexpressed AhR and colon tumor cell metabolism.},

note = {Place: Switzerland},

keywords = {AhR, Akt pathway, colon cancer cells, fatty acid synthesis, metabolism, proliferation},

pubstate = {published},

tppubtype = {article}

}

@article{rihova_transcription_2022,

title = {Transcription factor c-Myb: novel prognostic factor in osteosarcoma.},

author = {Kamila Říhová and Monika Dúcka and Iva Staniczková Zambo and Ladislava Vymětalová and Martin Šrámek and Filip Trčka and Jan Verner and Stanislav Drápela and Radek Fedr and Tereza Suchánková and Barbora Pavlatovská and Eva Ondroušková and Irena Kubelková and Danica Zapletalová and Štěpán Tuček and Peter Múdry and Dagmar Adámková Krákorová and Lucia Knopfová and Jan Šmarda and Karel Souček and Lubor Borsig and Petr Beneš},

doi = {10.1007/s10585-021-10145-4},

issn = {1573-7276 0262-0898},

year  = {2022},

date = {2022-04-01},

journal = {Clinical & experimental metastasis},

volume = {39},

number = {2},

pages = {375–390},

abstract = {The transcription factor c-Myb is an oncoprotein promoting cell proliferation and survival when aberrantly activated/expressed, thus contributing to malignant transformation. Overexpression of c-Myb has been found in leukemias, breast, colon and adenoid cystic carcinoma. Recent studies revealed its expression also in osteosarcoma cell lines and suggested its functional importance during bone development. However, the relevance of c-Myb in control of osteosarcoma progression remains unknown. A retrospective clinical study was carried out to assess a relationship between c-Myb expression in archival osteosarcoma tissues and prognosis in a cohort of high-grade osteosarcoma patients. In addition, MYB was depleted in metastatic osteosarcoma cell lines SAOS-2 LM5 and 143B and their growth, chemosensitivity, migration and metastatic activity were determined. Immunohistochemical analysis revealed that high c-Myb expression was significantly associated with poor overall survival in the cohort and metastatic progression in young patients. Increased level of c-Myb was detected in metastatic osteosarcoma cell lines and its depletion suppressed their growth, colony-forming capacity, migration and chemoresistance in vitro in a cell line-dependent manner. MYB knock-out resulted in reduced metastatic activity of both SAOS-2 LM5 and 143B cell lines in immunodeficient mice. Transcriptomic analysis revealed the c-Myb-driven functional programs enriched for genes involved in the regulation of cell growth, stress response, cell adhesion and cell differentiation/morphogenesis. Wnt signaling pathway was identified as c-Myb target in osteosarcoma cells. Taken together, we identified c-Myb as a negative prognostic factor in osteosarcoma and showed its involvement in the regulation of osteosarcoma cell growth, chemosensitivity, migration and metastatic activity.},

note = {Place: Netherlands},

keywords = {*Bone Neoplasms/pathology, *Osteosarcoma/pathology, Animals, c-Myb, Cell Line, Cell Movement/genetics, Cell Proliferation, Chemoresistance, Gene Expression Regulation, Humans, Metastasis, Mice, Neoplastic, Osteosarcoma, Prognosis, proliferation, Retrospective Studies, Tumor, Wnt Signaling Pathway},

pubstate = {published},

tppubtype = {article}

}

@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{simeckova_multiparameter_2018,

title = {Multiparameter cytometric analysis of complex cellular response.},

author = {Šárka Šimečková and Radek Fedr and Ján Remšík and Zuzana Kahounová and Eva Slabáková and Karel Souček},

doi = {10.1002/cyto.a.23295},

issn = {1552-4930 1552-4922},

year  = {2018},

date = {2018-02-01},

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

volume = {93},

number = {2},

pages = {239–248},

abstract = {Complex analysis of cellular responses after experimental treatment is important for screening, mechanistic understanding of treatment effects, and the identification of sensitive and resistant cell phenotypes. Modern multicolor flow cytometry has demonstrated its power for such analyses. Here, we introduce a multiparametric protocol for complex analysis of cytokinetics by the simultaneous detection of seven fluorescence parameters. This analysis includes the detection of two surface markers for immunophenotyping, analysis of proliferation based on the cell cycle and the measurement of incorporated nucleoside analogue 5-ethynyl-2'-deoxyuridine (EdU) in newly synthesized DNA, analysis of DNA damage using an anti-phospho-histone H2A.X (Ser139) antibody, and determination of cell death using a fixable viability probe and intracellular detection of caspase-3 activation. To demonstrate the applicability of this protocol for the analysis of heterogeneous and complex cell responses, we used different treatments and model cell lines. We demonstrated that this protocol has the potential to provide complex and simultaneous analysis of cytokinetics and analyze the heterogeneity of the response at the single-cell level. © 2017 International Society for Advancement of Cytometry.},

note = {Place: United States},

keywords = {Apoptosis, Apoptosis/*physiology, Cell Line, Cell Proliferation/*physiology, DNA Damage, DNA Damage/*physiology, Flow Cytometry, Flow Cytometry/*methods, Humans, immunophenotyping, Immunophenotyping/*methods, multiparametric analysis, proliferation, Tumor},

pubstate = {published},

tppubtype = {article}

}