Skip to main content

Metastability of proteins during tumor metastasis

Objective

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.

Call for proposal

ERC-2012-StG_20111109
See other projects for this call

Host institution

JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN
Address
Theodor W Adorno Platz 1
60323 Frankfurt Am Main
Germany
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 366 800
Principal investigator
Ramunas Martynas Vabulas (Dr.)
Administrative Contact
Kristina Wege (Ms.)

Beneficiaries (1)

JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN
Germany
EU contribution
€ 1 366 800
Address
Theodor W Adorno Platz 1
60323 Frankfurt Am Main
Activity type
Higher or Secondary Education Establishments
Principal investigator
Ramunas Martynas Vabulas (Dr.)
Administrative Contact
Kristina Wege (Ms.)