High mobility group box B (HMGB) proteins are overexpressed in different types of cancers such as epithelial ovarian cancers (EOC). We have determined the first interactome of HMGB1 and HMGB2 in epithelial ovarian cancer (the EOC-HMGB interactome). Libraries from the SKOV-3 cell line and a primary transitional cell carcinoma (TCC) ovarian tumor were tested by the Yeast Two Hybrid (Y2H) approach. The interactome reveals proteins that are related to cancer hallmarks and their expression is altered in EOC. Moreover, some of these proteins have been associated to survival and prognosis of patients. The interaction of MIEN1 and NOP53 with HMGB2 has been validated by co-immunoprecipitation in SKOV-3 and PEO1 cell lines. SKOV-3 cells were treated with different anti-tumoral drugs to evaluate changes in HMGB1, HMGB2, MIEN1 and NOP53 gene expression. Results show that combined treatment of paclitaxel and carboplatin induces a stronger down-regulation of these genes in comparison to individual treatments. Individual treatment with paclitaxel or olaparib up-regulates NOP53, which is expressed at lower levels in EOC than in non-cancerous cells. On the other hand, bevacizumab diminishes the expression of HMGB2 and NOP53. This study also shows that silencing of these genes affects cell-viability after drug exposure. HMGB1 silencing causes loss of response to paclitaxel, whereas silencing of HMGB2 slightly increases sensitivity to olaparib. Silencing of either HMGB1 or HMGB2 increases sensitivity to carboplatin. Lastly, a moderate loss of response to bevacizumab is observed when NOP53 is silenced.

Cancer cells try to avoid the overproduction of reactive oxygen species by metabolic rearrangements. These cells also develop specific strategies to increase ROS resistance and to express the enzymatic activities necessary for ROS detoxification. Oxidative stress produces DNA damage and also induces responses, which could help the cell to restore the initial equilibrium. But if this is not possible, oxidative stress finally activates signals that will lead to cell death. High mobility group B (HMGB) proteins have been previously related to the onset and progressions of cancers of different origins. The protein HMGB1 behaves as a redox sensor and its structural changes, which are conditioned by the oxidative environment, are associated with different functions of the protein. This review describes recent advances in the role of human HMGB proteins and other proteins interacting with them, in cancerous processes related to oxidative stress, with special reference to ovarian and prostate cancer. Their participation in the molecular mechanisms of resistance to cisplatin, a drug commonly used in chemotherapy, is also revised.

High mobility group box B (HMGB) proteins are pivotal in the development of cancer. Although the proteomics of prostate cancer (PCa) cells has been reported, the involvement of HMGB proteins and their interactome in PCa is an unexplored field of considerable interest. We describe herein the results of the first HMGB1/HMGB2 interactome approach to PCa. Libraries constructed from the PCa cell line, PC-3, and from patients' PCa primary tumor have been screened by the yeast 2-hybrid approach (Y2H) using HMGB1 and HMGB2 baits. Functional significance of this PCa HMGB interactome has been validated through expression and prognosis data available on public databases. Copy number alterations (CNA) affecting these newly described HMGB interactome components are more frequent in the most aggressive forms of PCa: those of neuroendocrine origin or castration-resistant PCa. Concordantly, adenocarcinoma PCa samples showing CNA in these genes are also associated with the worse prognosis. These findings open the way to their potential use as discriminatory biomarkers between high and low risk patients. Gene expression of a selected set of these interactome components has been analyzed by qPCR after HMGB1 and HMGB2 silencing. The data show that HMGB1 and HMGB2 control the expression of several of their interactome partners, which might contribute to the orchestrated action of these proteins in PCa.

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.