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

Faiz M. Khan, Stephan Marquardt, Shailendra K. Gupta, Susanne Knoll, Ulf Schmitz, Alf Spitschak, David Engelmann, Julio Vera (), Olaf Wolkenhauer and Brigitte M. Pützer
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Faiz M. Khan: University of Rostock
Stephan Marquardt: Rostock University Medical Center
Shailendra K. Gupta: University of Rostock
Susanne Knoll: Rostock University Medical Center
Ulf Schmitz: University of Rostock
Alf Spitschak: Rostock University Medical Center
David Engelmann: Rostock University Medical Center
Julio Vera: Erlangen University Hospital and FAU University of Erlangen-Nuremberg
Olaf Wolkenhauer: University of Rostock
Brigitte M. Pützer: Rostock University Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00268-2

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