Latest Publications

@article{hyzdalova_transcriptional_2024,

title = {Transcriptional and phenotypical alterations associated with a gradual benzo[a]pyrene-induced transition of human bronchial epithelial cells into mesenchymal-like cells.},

author = {Martina Hýžďalová and Jiřina Procházková and Nicol Straková and Kateřina Pěnčíková and Simona Strapáčová and Jana Slováčková and Simona Kajabová and Helena Líbalová and Jan Topinka and Markéta Kabátková and Jan Vondráček and Steen Mollerup and Miroslav Machala},

doi = {10.1016/j.etap.2024.104424},

issn = {1872-7077 1382-6689},

year  = {2024},

date = {2024-04-01},

journal = {Environmental toxicology and pharmacology},

volume = {107},

pages = {104424},

abstract = {The role of benzo[a]pyrene (BaP), a prominent genotoxic carcinogen and aryl hydrocarbon receptor (AhR) ligand, in tumor progression remains poorly characterized. We investigated the impact of BaP on the process of epithelial-mesenchymal transition (EMT) in normal human bronchial epithelial HBEC-12KT cells. Early morphological changes after 2-week exposure were accompanied with induction of SERPINB2, IL1, CDKN1A/p21 (linked with cell cycle delay) and chemokine CXCL5. After 8-week exposure, induction of cell migration and EMT-related pattern of markers/regulators led to induction of further pro-inflammatory cytokines or non-canonical Wnt pathway ligand WNT5A. This trend of up-regulation of pro-inflammatory genes and non-canonical Wnt pathway constituents was observed also in the BaP-transformed HBEC-12KT-B1 cells. In general, transcriptional effects of BaP differed from those of TGFβ1, a prototypical EMT inducer, or a model non-genotoxic AhR ligand, TCDD. Carcinogenic polycyclic aromatic hydrocarbons could thus induce a unique set of molecular changes linked with EMT and cancer progression.},

note = {Place: Netherlands},

keywords = {*Benzo(a)pyrene/toxicity, *Epithelial Cells/metabolism, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, Aryl hydrocarbon receptor, Aryl Hydrocarbon/genetics/metabolism, Benzo[a]pyrene, DNA Damage, Epithelial-Mesenchymal Transition, Human bronchial epithelial cells, Humans, Ligands, Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{slabakova_opposite_2015,

title = {Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal phenotype in benign and cancer cells.},

author = {Eva Slabáková and Gvantsa Kharaishvili and Monika Smějová and Zuzana Pernicová and Tereza Suchánková and Ján Remšík and Stanislav Lerch and Nicol Straková and Jan Bouchal and Milan Král and Zoran Culig and Alois Kozubík and Karel Souček},

doi = {10.18632/oncotarget.5392},

issn = {1949-2553},

year  = {2015},

date = {2015-11-01},

journal = {Oncotarget},

volume = {6},

number = {34},

pages = {36156–36171},

abstract = {Plasticity of cancer cells, manifested by transitions between epithelial and mesenchymal phenotypes, represents a challenging issue in the treatment of neoplasias. Both epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are implicated in the processes of metastasis formation and acquisition of stem cell-like properties. Mouse double minute (MDM) 2 and MDMX are important players in cancer progression, as they act as regulators of p53, but their function in EMT and metastasis may be contradictory. Here, we show that the EMT phenotype in multiple cellular models and in clinical prostate and breast cancer samples is associated with a decrease in MDM2 and increase in MDMX expression. Modulation of EMT-accompanying changes in MDM2 expression in benign and transformed prostate epithelial cells influences their migration capacity and sensitivity to docetaxel. Analysis of putative mechanisms of MDM2 expression control demonstrates that in the context of defective p53 function, MDM2 expression is regulated by EMT-inducing transcription factors Slug and Twist. These results provide an alternative context-specific role of MDM2 in EMT, cell migration, metastasis, and therapy resistance.},

note = {Place: United States},

keywords = {Animals, Breast Neoplasms/genetics/*metabolism/pathology, Cell Cycle Proteins, Cell Line, Epithelial-Mesenchymal Transition, Epithelial-Mesenchymal Transition/*physiology, Female, Heterografts, Humans, Male, MDM2/MDMX, Mice, Nuclear Proteins/*biosynthesis, Nude, Phenotype, prostate/breast cancer, Prostatic Neoplasms/genetics/*metabolism/pathology, Proto-Oncogene Proteins c-mdm2/*biosynthesis, Proto-Oncogene Proteins/*biosynthesis, Snai2/Slug, Transfection, Tumor, TWIST},

pubstate = {published},

tppubtype = {article}

}