ONCROBUST
Unravelling oncogenic defects in feedback control of receptor tyrosine kinases
| Coordinatore | WEIZMANN INSTITUTE OF SCIENCE
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | Israel [IL] |
| Totale costo | 2˙228˙180 € |
| EC contributo | 2˙228˙180 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2010-AdG_20100317 |
| Funding Scheme | ERC-AG |
| Anno di inizio | 2011 |
| Periodo (anno-mese-giorno) | 2011-08-01 - 2016-07-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
WEIZMANN INSTITUTE OF SCIENCE
Organization address
address: HERZL STREET 234 contact info |
IL (REHOVOT) | hostInstitution | 2˙228˙180.00 |
| 2 |
WEIZMANN INSTITUTE OF SCIENCE
Organization address
address: HERZL STREET 234 contact info |
IL (REHOVOT) | hostInstitution | 2˙228˙180.00 |
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Obiettivo del progetto (Objective)
'Cellular growth and migration depend on intracellular communication webs mediated by polypeptide growth factors. One example comprises EGF-like growth factors and their ErbB receptor tyrosine kinases. EGFR and HER2 are frequently involved in cancer progression, and they serve as targets for cancer therapeutics. The existence of a kinase-dead receptor, as well as the emergence of resistance in patients treated with EGFR and HER2 blockers, instigated a paradigm shift from a linear EGF-to-ErbB cascade to a robust network characterized by multiple feedback loops. We assume that deregulation of feedback loops plays essential roles in human cancer. Because of the abundance of feedback regulation, we predict subtle, multi-component impact on disease. Aiming at the natural richness of feedback regulation in breast cancer, we will develop in vitro models of normal mammary cells, and introduce genetic, disease-mimicry manipulations. Two time domains of feedback regulation will be addressed: (i) the early domain of post-translational modifications, which we will explore using proteomic approaches. And (ii) the late domain comprising alterations in transcription, micro-RNAs and alternative splicing, processes we will investigate using deep sequencing and array technologies. Once verified and characterized in normal cells, we will survey the operational status of the unravelled feedback loops in genetically manipulated cell systems and in tumour specimens, using immunological and bio-informatical approaches. Detailed knowledge of feedback regulation of multi-layered signalling networks, such as ErbB, is expected to shed light on the currently elusive basis of signal integration and elimination of noise, as well as identify markers of prognosis.'