Cel 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. Dziedzina nauki medical and health sciencesclinical medicineoncologybreast cancer Program(-y) 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) Temat(-y) ERC-AG-ID1 - ERC Advanced Grant Interdisciplinary Panel Zaproszenie do składania wniosków ERC-2010-AdG_20100317 Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-AG - ERC Advanced Grant Instytucja przyjmująca WEIZMANN INSTITUTE OF SCIENCE Wkład UE € 2 228 180,00 Adres HERZL STREET 234 7610001 Rehovot Izrael Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Gabi Bernstein (Ms.) Kierownik naukowy Yosef Yarden (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko WEIZMANN INSTITUTE OF SCIENCE Izrael Wkład UE € 2 228 180,00 Adres HERZL STREET 234 7610001 Rehovot Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Gabi Bernstein (Ms.) Kierownik naukowy Yosef Yarden (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych