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Interruption of protein-protein interaction and network to cancer biomarkers and therapeutic targets

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Cancer-causing protein interactions

Cancer affects millions of people globally, with prostate and glioblastoma multiforme (GBM) cancers causing major fatalities. EU-funded researchers studied cancer-causing alterations in protein-protein interaction and gene networks for these cancers.


Cancer is highly complex and a result of genomic perturbations that promote cancer cell survival through alterations in several cellular mechanisms, including apoptosis and DNA repair. Scientists have managed to obtain some insight into the underlying molecular mechanisms. Understanding the protein-protein interactions and gene regulatory networks that are affected in cancer initiation, progression and drug response could be the key to finding therapeutic solutions. The goal of the PPI-MARKER (Interruption of protein-protein interaction and network to cancer biomarkers and therapeutic targets) project was to use gain or loss of protein-protein interactions to reveal their role in tumour development. Researchers used a network-based approach to find biomarkers for prostate and GBM cancers. For this purpose, they combined gene expression data with protein-protein interactions or regulatory transcriptional networks. Their area of focus was the androgen receptor protein-protein network in prostate cancer and the TGF-beta-mediated network in gliomas. ChIP-Chip and ChIP-Seq experiments on patient cancer samples helped identify the key transcription factors and their targets. They used a novel technique called metaDBSite to pinpoint relevant network motifs and modules. As a result, they successfully elucidated the role of IL-6 and the downstream STAT3 signalling as well as elevated reactive oxygen species in prostate cancer initiation. PPI-MARKER further investigated promising biomarker candidates and validated them experimentally. Some of these candidates were also modelled using protein structural data on protein-protein complexes. This should aid in designing ligands that disrupt cancer-relevant interactions by occupying the associated binding sites. Prostate cancer is the number one killer among men in developed countries and GBM is the most common aggressive form of primary brain tumour. Project activities have made significant inroads towards diagnosing and designing therapeutic solutions for these cancers.


Cancer, prostate, glioblastoma multiforme, protein-protein interaction, gene networks, biomarkers

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