Abstract

Abstract Nuclear transport is an essential, highly selective process in eukaryotic cells which guarantees the bidirectional communication between the nucleus and the cytoplasm. Emerging evidence suggests that aberrant expression of nuclear transport factors may contribute to cancer formation and progression. We could recently show that the nuclear exporter Cellular apoptosis susceptibility (CAS) is overexpressed in hepatocellular carcinoma (HCC), the functional implications of which remain, however, not completely understood. Here, we integrated proteomics, transcriptomics and functional assays with patient data to further characterize the role of CAS in HCC. We found that CAS depletion in HCC cells led to deregulation of integrins, particularly integrin-beta1, and resulted in reduced cell migration and invasion. Moreover, we determined that high expression levels of CAS in HCC cases were associated with macroangioinvasion and poorer patient outcome. Our data indicate that CAS is linked to integrin signaling and correlates with an aggressive HCC phenotype. Citation Format: Juliane Winkler, Carsten Sticht, Amanda DiGuilio, Eva Maria Eiteneuer, Kerstin Holzer, Stephanie Rössler, Norbert Gretz, Kai Breuhahn, Peter Schirmacher, Alessandro Ori, Stephan Singer. Cellular apoptosis susceptibility (CAS) regulates integrin-beta1 and is required for tumor cell migration and invasion in hepatocellular carcinoma (HCC). [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A46.

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