Is cell cycle arrest imperative for AhR signaling-mediated induction of EMT phenotype in lung adenocarcinoma cells?

Kód výsledku v IS VaVaI

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Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Is cell cycle arrest imperative for AhR signaling-mediated induction of EMT phenotype in lung adenocarcinoma cells?

Popis výsledku v původním jazyce

AHR meeting, Paris 2018, 28.-31.8.2018 – poster. Environmental pollutants, e.g. components of cigarette smoke, herbicides and airborne particles, had been previously documented as potent inducers of AhR signaling in lung tissue. Although several reports provide indications that AhR signaling play important role in the progression and dissemination of lung primary tumors, the mechanism of this process remains rather elusive. Herein, we employed well-annotated in vitro model of lung carcinoma cells A549 and investigated their cellular fate after chronic exposure to model agonistic AhR ligands (benzo[a]pyrene - BaP, TCDD). While global gene expression data were similar after short-term (24 h) exposure to BaP and TCDD, significantly different gene expression pattern and fate of the cells was found after prolonged (14 days) exposure. In comparison with cells exposed to TCDD, cells exposed to BaP underwent cellular transformation and switched from epithelial to mesenchymal phenotype. Observed transformation was associated with enhancement of migratory potential and with changes in expression pattern of EMT markers (E-cadherin, N-cadherin, Snail-1). Global profiling of A549 transcriptome point to several biological processes recruited during cell cycling and division and prompted us to investigate more deeply the role of cell cycle arrest in induction of EMT. Indeed, when we induced cell cycle arrest and EMT by treatment of A549 with mitomycin, co-treatment of cells with both mitomycin and TCDD enhanced expression of EMT markers and boosted migratory potential of the cells. Considering the fact that BaP as a genotoxic compound triggers cell cycle arrest by p53-mediated induction of p21 expression, we next explored the role of this cell cycle-dependent kinase inhibitor in induction of EMT using lentiviral delivery of targeted shRNA molecules cloned into commercial pLKO vectors.

Název v anglickém jazyce

Is cell cycle arrest imperative for AhR signaling-mediated induction of EMT phenotype in lung adenocarcinoma cells?

Popis výsledku anglicky

AHR meeting, Paris 2018, 28.-31.8.2018 – poster. Environmental pollutants, e.g. components of cigarette smoke, herbicides and airborne particles, had been previously documented as potent inducers of AhR signaling in lung tissue. Although several reports provide indications that AhR signaling play important role in the progression and dissemination of lung primary tumors, the mechanism of this process remains rather elusive. Herein, we employed well-annotated in vitro model of lung carcinoma cells A549 and investigated their cellular fate after chronic exposure to model agonistic AhR ligands (benzo[a]pyrene - BaP, TCDD). While global gene expression data were similar after short-term (24 h) exposure to BaP and TCDD, significantly different gene expression pattern and fate of the cells was found after prolonged (14 days) exposure. In comparison with cells exposed to TCDD, cells exposed to BaP underwent cellular transformation and switched from epithelial to mesenchymal phenotype. Observed transformation was associated with enhancement of migratory potential and with changes in expression pattern of EMT markers (E-cadherin, N-cadherin, Snail-1). Global profiling of A549 transcriptome point to several biological processes recruited during cell cycling and division and prompted us to investigate more deeply the role of cell cycle arrest in induction of EMT. Indeed, when we induced cell cycle arrest and EMT by treatment of A549 with mitomycin, co-treatment of cells with both mitomycin and TCDD enhanced expression of EMT markers and boosted migratory potential of the cells. Considering the fact that BaP as a genotoxic compound triggers cell cycle arrest by p53-mediated induction of p21 expression, we next explored the role of this cell cycle-dependent kinase inhibitor in induction of EMT using lentiviral delivery of targeted shRNA molecules cloned into commercial pLKO vectors.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10601 - Cell biology

Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů