Objective
Chromosomal instability (CIN), the inability to correctly segregate sister chromatids during mitosis, is a hallmark of cancer cells. Overexpression of the mitotic checkpoint protein Mad2, commonly found in human tumors, leads to CIN and the development of aneuploid tumors in mouse models. However, recent observations from various laboratories suggest that aneuploidy can promote or suppress tumorigenesis. Therefore understanding the relationship between aneuploidy and tumor formation, identifying in what context aneuploidy acts oncogenically and those in which it acts as a tumor suppressor, is thus vital if we want to make progress in battling cancer. We propose to generate regulatable mouse models that recapitulate the aneuploidy state of human tumors, using state-of–the–art mouse genetic strategies, to investigate the role of CIN in promoting or suppressing tumorigenesis.
Moreover, CIN has been shown to facilitate escape from oncogene addiction (the dependence of tumor cells on their initiating lesion for survival) and may be responsible for tumor relapse after targeted therapies. Due to the clinical relevance of these findings, this proposal aims to investigate how CIN potentiates oncogene independence. It is possible that some CIN cells in the primary tumor are already independent of the initiating oncogene prior to treatment. Alternatively, CIN cells are more susceptible of acquiring additional mutations and evolve to become independent of the initiating lesion. We propose to develop a highly innovative three-dimensional in vitro culture system to isolate and characterize these surviving cells to further eliminate them.
It is necessary to understand the molecular mechanisms that lead to CIN and the consequences it has in tumor initiation, suppression and relapse, hoping that the genes or proteins identified could be targeted therapeutically. We believe that answers to these specific aims will have important consequences for the treatment of human tumors.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2011-StG_20101109
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
69120 Heidelberg
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.