期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-017-00268-2
关键词
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资金
- German Federal Ministry of Education and Research (BMBF) as part of the project eBio:SysMet [0316171]
- eBio: MelEVIR [031L0073A, 031L0073B]
- German Cancer Aid
- Dr Mildred Scheel Stiftung [109801]
- Rostock University Medical Faculty for the project Systems Medicine of Cancer Invasion and Metastasis
- Erlangen University Hospital (ELAN funds) [14-07-22-1-Vera-Gonzalez]
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-pecific 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.
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