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Integrin alpha-V drives pancreatic adenocarcinoma progression due to activation of TGF-β

ABSTRACT: In a previous study by our group, it could be shown that peritoneal selectins mediate the peritoneal spread of pancreatic ductal adenocarcinoma (PDA). In the absence of selectins, Integrin alpha-V (ITGAV) is upregulated in the remaining tumor spots. To study the relevance of ITGAV for PDA’s progression, a knockdown of ITGAV was generated using a shRNA-mediated approach in two PDA cell lines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153702 | GEO | 2020/07/31

REPOSITORIES: GEO

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Project description:Geier2011 - Integrin activation Rule based model that integrates the available data to test the biololical hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. This model is described in the article: A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation. Geier F, Fengos G, Iber D. PLoS One. 2011;6(11):e24808. Abstract: Integrin signaling regulates cell migration and plays a pivotal role in developmental processes and cancer metastasis. Integrin signaling has been studied extensively and much data is available on pathway components and interactions. Yet the data is fragmented and an integrated model is missing. We use a rule-based modeling approach to integrate available data and test biological hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. The detailed biochemical characterization of integrin signaling provides us with measured values for most of the kinetics parameters. However, measurements are not fully accurate and the cellular concentrations of signaling proteins are largely unknown and expected to vary substantially across different cellular conditions. By sampling model behaviors over the physiologically realistic parameter range we find that the model exhibits only two different qualitative behaviors and these depend mainly on the relative protein concentrations, which offers a powerful point of control to the cell. Our study highlights the necessity to characterize model behavior not for a single parameter optimum, but to identify parameter sets that characterize different signaling modes. This model is hosted on BioModels Database and identified by: MODEL1208280001 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Integrin alpha-V drives pancreatic adenocarcinoma progression due to activation of TGF-β

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