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• W2344702307 abstract "// Juliane Winkler 1 , Stephanie Roessler 1 , Carsten Sticht 2 , Amanda L. DiGuilio 3 , Elisabeth Drucker 1 , Kerstin Holzer 1 , Eva Eiteneuer 1 , Esther Herpel 1, 4 , Kai Breuhahn 1 , Norbert Gretz 2 , Peter Schirmacher 1 , Alessandro Ori 5, 6 , Stephan Singer 1, 5 1 Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany 2 Medical Research Centre, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany 3 Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA 4 Tissue Bank of the National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany 5 European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Heidelberg, Germany 6 Leibniz Institute on Aging - Fritz-Lipmann-Institute e.V. (FLI), Jena, Germany Correspondence to: Stephan Singer, e-mail: stephan.singer@med.uni-heidelberg.de Keywords: HCC, CAS, integrin β1, migration, nuclear transport Received: October 14, 2015      Accepted: February 23, 2016      Published: March 23, 2016 ABSTRACT Importins and exportins represent an integral part of the nucleocytoplasmic transport machinery with fundamental importance for eukaryotic cell function. A variety of malignancies including hepatocellular carcinoma (HCC) show de-regulation of nuclear transport factors such as overexpression of the exportin Cellular Apoptosis Susceptibility (CAS). The functional implications of CAS in hepatocarcinogenesis remain, however, poorly understood. Here we integrated proteomics, transcriptomics and functional assays with patient data to further characterize the role of CAS in HCC. By analyzing ~ 1700 proteins using quantitative mass spectrometry in HCC cells we found that CAS depletion by RNA i leads to de-regulation of integrins, particularly down-regulation of integrin β1. Consistent with this finding, CAS knockdown resulted in substantially reduced migration and invasion of HCC cell lines as analyzed by 2D ‘scratch’ and invasion chamber assays, respectively. Supporting the potential in vivo relevance, high expression levels of CAS in HCC tissue samples were associated with macroangioinvasion and poorer patient outcome. Our data suggest a previously unanticipated link between CAS and integrin signaling which correlates with an aggressive HCC phenotype." @default.
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• W2344702307 date "2016-03-23" @default.
• W2344702307 modified "2023-10-12" @default.
• W2344702307 title "Cellular apoptosis susceptibility (CAS) is linked to integrin β1 and required for tumor cell migration and invasion in hepatocellular carcinoma (HCC)" @default.
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• W2344702307 doi "https://doi.org/10.18632/oncotarget.8256" @default.
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