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Intracellular free zinc mediates compressive stress-induced mechanotransduction in pancreatic cancer

ABSTRACT: In this study, Nihei et al. show that unknown function of the intracellular free zinc in mechanical compressive stress-induced signaling and altered gene expression in pancreatic cancer cells, provide novel perspectives on zinc as a signal transducer and therapeutic target. We explored the roles of compressive stress in pancreatic cancer progression by investigating the changes in gene expression induced by it using microarray.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196275 | GEO | 2022/08/01

REPOSITORIES: GEO

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Project description:This a model from the article: The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress Takahashi H, Oshima T, Doherty N, Clayton SR, Iqbal M, Hill PJ, Hobman JL, Tobe T, Ogasawara N, Kanaya S and Stekel DJ journal year id, Abstract: Zinc is essential for life, but toxic in excess. Thus all cells must control their internal zinc concentration. We used a systems approach, alternating rounds of experiments and models, to further elucidate the zinc control systems in Escherichia coli. We measured the response to zinc of the main specific zinc import and export systems in the wild type, and a series of deletion mutant strains. We interpreted these data with a detailed mathematical model and Bayesian model fitting routines. There are three key findings: First, that alternate, non-inducible importers and exporters are important. Second, that an internal zinc reservoir is essential for maintaining the internal zinc concentration. Third, our data fitting led us to propose that the cells mount a heterogeneous response to zinc: some respond effectively, while others die or stop growing. In a further round of experiments we demonstrated lower viable cell counts in the mutant strain tested exposed to excess zinc, consistent with this hypothesis. A stochastic model simulation demonstrated considerable fluctuations in the cellular levels of the ZntA exporter protein, reinforcing this proposal. We hypothesise that maintaining population heterogeneity could be a bet-hedging response allowing a population of cells to survive in varied and fluctuating environments. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le NovÃ¨re N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

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Intracellular free zinc mediates compressive stress-induced mechanotransduction in pancreatic cancer

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