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Role of the PDZ-scaffold protein NHERF1/EBP50 in cancer biology: from signaling regulation to clinical relevance

Abstract

The transmission of cellular information requires fine and subtle regulation of proteins that need to interact in a coordinated and specific way to form efficient signaling networks. The spatial and temporal coordination relies on scaffold proteins. Thanks to protein interaction domains such as PDZ domains, scaffold proteins organize multiprotein complexes enabling the proper transmission of cellular information through intracellular networks. NHERF1/EBP50 is a PDZ-scaffold protein that was initially identified as an organizer and regulator of transporters and channels at the apical side of epithelia through actin-binding ezrin-moesin-radixin proteins. Since, NHERF1/EBP50 has emerged as a major regulator of cancer signaling network by assembling cancer-related proteins. The PDZ-scaffold EBP50 carries either anti-tumor or pro-tumor functions, two antinomic functions dictated by EBP50 expression or subcellular localization. The dual function of NHERF1/EBP50 encompasses the regulation of several major signaling pathways engaged in cancer, including the receptor tyrosine kinases PDGFR and EGFR, PI3K/PTEN/AKT and Wnt-β-catenin pathways.

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Acknowledgements

THB was supported by the ‘Ministère de l’Enseignement Supérieur et de la Recherche’, Fondation de France No. 2011-00025574 and Fondation ARC No. DOC20130606463. LF is supported by grants from Fondation de France (No. 2014 00047502), La Ligue National contre le Cancer (No. RS14/75-112) and GEFLUC. JV is recipient of two following postdoctoral fellowships from the Spanish Association for the Study of the Liver (AEEH) and the Fondation ARC No. PDF2014601431. The authors thank Yves Chrétien for the graphic support.

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Vaquero, J., Nguyen Ho-Bouldoires, T., Clapéron, A. et al. Role of the PDZ-scaffold protein NHERF1/EBP50 in cancer biology: from signaling regulation to clinical relevance. Oncogene 36, 3067–3079 (2017). https://doi.org/10.1038/onc.2016.462

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