Skip to main content
European Commission logo
Deutsch Deutsch
CORDIS - Forschungsergebnisse der EU
CORDIS
CORDIS Web 30th anniversary CORDIS Web 30th anniversary
Inhalt archiviert am 2024-06-18

Unravelling oncogenic defects in feedback control of receptor tyrosine kinases

Ziel

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.

Aufforderung zur Vorschlagseinreichung

ERC-2010-AdG_20100317
Andere Projekte für diesen Aufruf anzeigen

Gastgebende Einrichtung

WEIZMANN INSTITUTE OF SCIENCE
EU-Beitrag
€ 2 228 180,00
Adresse
HERZL STREET 234
7610001 Rehovot
Israel

Auf der Karte ansehen

Aktivitätstyp
Higher or Secondary Education Establishments
Kontakt Verwaltung
Gabi Bernstein (Ms.)
Hauptforscher
Yosef Yarden (Prof.)
Links
Gesamtkosten
Keine Daten

Begünstigte (1)