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

Journal Publication ResearchOnline@JCU
Khan, Faiz M.;Marquardt, Stephan;Gupta, Shailendra K.;Knoll, Susanne;Schmitz, Ulf;Spitschak, Alf;Engelmann, David;Vera, Julio;Wolkenhauer, Olaf;Pützer, Brigitte M.
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.

Journal

Nature Communications

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Volume

8

ISBN/ISSN

2041-1723

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Pages Count

15

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Publisher

Nature Publishing Group

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DOI

10.1038/s41467-017-00268-2