Cel Mutational heterogeneity bestows tumors with the phenotypic plasticity and adaptability required for expansion. On the other hand, mutations destabilize proteins – lower stability (metastability) of the tumor proteome must be the inevitable consequence. We set out to systematically investigate this biochemical aspect of metastasis aiming to uncover and therapeutically exploit specific vulnerabilities resulting from protein destabilization. We will approach this goal by cataloging associations between metastasis-promoting proteins and molecular chaperones. Chaperones are obvious candidates to stabilize the proteome, therefore we will prepare a BAC-based mouse model of metastasis, where the contribution of 63 chaperones, comprising the entire murine HSP70 superfamily, to metastasis development will be individually investigated. The role of metastasis-relevant chaperones at the molecular level will be elucidated using mass spectrometry, complemented by next-generation sequencing of metastatic exome. In parallel, a novel proteomics-based method to evaluate aberrant complex formation in tumor cells will be established.Because of the high heterogeneity of cancer, molecularly tailored and combined therapies are needed. To this end, we will capitalize on insights regarding the role of chaperones in metastasis by identifying proteasomal degradation activators able to support or replace the activity of individual chaperones from the HSP70 superfamily. Finally, we will validate the potential of combined, yet specific manipulation of the folding and degradation machineries to suppress metastasis development. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologynatural scienceschemical sciencesanalytical chemistrymass spectrometry 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-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Zaproszenie do składania wniosków ERC-2012-StG_20111109 Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-SG - ERC Starting Grant Instytucja przyjmująca JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN Wkład UE € 1 366 800,00 Adres THEODOR W ADORNO PLATZ 1 60323 Frankfurt Am Main Niemcy Zobacz na mapie Region Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Kristina Wege (Ms.) Kierownik naukowy Ramunas Martynas Vabulas (Dr.) 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 JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN Niemcy Wkład UE € 1 366 800,00 Adres THEODOR W ADORNO PLATZ 1 60323 Frankfurt Am Main Zobacz na mapie Region Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Kristina Wege (Ms.) Kierownik naukowy Ramunas Martynas Vabulas (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych