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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.

Author information

1
Department of Systems Biology and Bioinformatics, University of Rostock, 18051, Rostock, Germany.
2
Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, 18057, Rostock, Germany.
3
Department of Bioinformatics, CSIR-Indian Institute of Toxicology Research, Lucknow, 206001, India.
4
Gene & Stem Cell Therapy Program, Centenary Institute, Camperdown, NSW, 2050, Australia.
5
Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia.
6
Department of Dermatology, Laboratory of Systems Tumor Immunology, Erlangen University Hospital and FAU University of Erlangen-Nuremberg, 91054, Erlangen, Germany. Julio.Vera-Gonzalez@uk-erlangen.de.
7
Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, 7600, South Africa.

Abstract

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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