Delineating the HMGB1 and HMGB2 interactome in prostate and ovary epithelial cells and its relationship with cancer

// Aida Barreiro-Alonso 1 , Monica Lamas-Maceiras 1 , Rosa Garcia-Diaz 1 , Esther Rodriguez-Belmonte 1 , Lu Yu 2, 3 , Mercedes Pardo 2, 3 , Jyoti S. Choudhary 2, 3 and Maria Esperanza Cerdan 1 1 EXPRELA Group, Centro de Investigacions Cientificas Avanzadas, Departamento de Biologia, Facultade de Ciencias, INIBIC-Universidade da Coruna, Campus de A Coruna, A Coruna, 15071, Spain 2 Proteomic Mass Spectrometry, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom 3 Present Address: The Institute of Cancer Research, Chester Beatty Laboratories, London, SW3 6JB, United Kingdom Correspondence to: Maria Esperanza Cerdan, email: esper.cerdan@udc.es Keywords: epithelial cells; high mobility proteins; protein-protein interactions; HMGB1; HMGB2 Received: November 03, 2017      Accepted: February 27, 2018      Published: April 10, 2018 ABSTRACT High Mobility Group B (HMGB) proteins are involved in cancer progression and in cellular responses to platinum compounds used in the chemotherapy of prostate and ovary cancer. Here we use affinity purification coupled to mass spectrometry (MS) and yeast two-hybrid (Y2H) screening to carry out an exhaustive study of HMGB1 and HMGB2 protein interactions in the context of prostate and ovary epithelia. We present a proteomic study of HMGB1 partners based on immunoprecipitation of HMGB1 from a non-cancerous prostate epithelial cell line. In addition, HMGB1 and HMGB2 were used as baits in yeast two-hybrid screening of libraries from prostate and ovary epithelial cell lines as well as from healthy ovary tissue. HMGB1 interacts with many nuclear proteins that control gene expression, but also with proteins that form part of the cytoskeleton, cell-adhesion structures and others involved in intracellular protein translocation, cellular migration, secretion, apoptosis and cell survival. HMGB2 interacts with proteins involved in apoptosis, cell motility and cellular proliferation. High confidence interactors, based on repeated identification in different cell types or in both MS and Y2H approaches, are discussed in relation to cancer. This study represents a useful resource for detailed investigation of the role of HMGB1 in cancer of epithelial origins, as well as potential alternative avenues of therapeutic intervention.