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Nat Commun. 2017 Aug 4;8(1):198. doi: 10.1038/s41467-017-00268-2.

Unraveling a tumor type-specific regulatory core underlying E2F1-mediated epithelial-mesenchymal transition to predict receptor protein signatures.

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Department of Systems Biology and Bioinformatics, University of Rostock, 18051, Rostock, Germany.
Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, 18057, Rostock, Germany.
Department of Bioinformatics, CSIR-Indian Institute of Toxicology Research, Lucknow, 206001, India.
Gene & Stem Cell Therapy Program, Centenary Institute, Camperdown, NSW, 2050, Australia.
Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia.
Department of Dermatology, Laboratory of Systems Tumor Immunology, Erlangen University Hospital and FAU University of Erlangen-Nuremberg, 91054, Erlangen, Germany.
Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, 7600, South Africa.


Cancer is a disease of subverted regulatory pathways. In this paper, we reconstruct the regulatory network around E2F, a family of transcription factors whose deregulation has been associated to cancer progression, chemoresistance, invasiveness, and metastasis. We integrate gene expression profiles of cancer cell lines from two E2F1-driven highly aggressive bladder and breast tumors, and use network analysis methods to identify the tumor type-specific core of the network. By combining logic-based network modeling, in vitro experimentation, and gene expression profiles from patient cohorts displaying tumor aggressiveness, we identify and experimentally validate distinctive, tumor type-specific signatures of receptor proteins associated to epithelial-mesenchymal transition in bladder and breast cancer. Our integrative network-based methodology, exemplified in the case of E2F1-induced aggressive tumors, has the potential to support the design of cohort- as well as tumor type-specific treatments and ultimately, to fight metastasis and therapy resistance.Deregulation of E2F family transcription factors is associated with cancer progression and metastasis. Here, the authors construct a map of the regulatory network around the E2F family, and using gene expression profiles, identify tumour type-specific regulatory cores and receptor expression signatures associated with epithelial-mesenchymal transition in bladder and breast cancer.

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