Objective
Constitutive activation of the Wnt pathway is the key step for initiation of colorectal cancer (CRC). Wnt signaling also plays an essential role in the maintenance of intestinal stem cells (ISCs). In addition, acquisition of a constitutive crypt stem/progenitor phenotype represents the first step towards malignancy. The identification of the Wnt target gene Lgr5 as a marker for ISCs and the finding that Lgr5+ ISCs represent the origin of intestinal cancer suggest that specific features of ISC are required to initiate CRC. Given the critical role of ISCs in CRC onset, we intend to study their contribution to CRC progression, tumor recurrence, and metastasis. Characterization of Lgr5+ CRC cells at different disease stages will clarify, which part of the “stemness” genetical program remains conserved during progression of malignancy. We will also address to which extent an Lgr5+ CRC cell residing in a primary tumor or in metastasis resembles a crypt Lgr5+ ISC. To achieve this, progression of intestinal cancer derived from ISCs or differentiated cells will be studied using a novel transgenic mouse model system: Starting from defined, targeted cells which have acquired Wnt activation combined with mutation in KRAS, tumor progression can be tracked by fluorescent proteins concomitantly induced with compound mutations. “State-of the art” flow-cytometry-based sorting techniques will be used to isolate different tumor sub-populations in order to characterize them in detail. Interestingly, only a rare sub-population of tumor cells in CRC patients, so-called “cancer stem cells” (CSCs), is able to re-establish tumor growth in immune-deficient animals. We seek to understand how these tumor-promoting cells are genetically and functionally related to Lgr5+ ISC and Lgr5+ cells in CRC. Our results will achieve significant advancement in understanding the relationship between CSCs and ISCs and hold potential for the future development of both therapeutic and diagnostic tools.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology colorectal cancer
- natural sciences biological sciences genetics mutation
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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.
FP7-PEOPLE-2009-IEF
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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.
Coordinator
08028 Barcelona
Spain
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.