Objective
Adenomatous polyposis coli (APC) is an important tumour suppressor in the human colon epithelium: its loss of function is known to be a primary cause of tumourigenesis, accounting for more than 80% of all heritable and spontaneous colon cancers.
The first significant clue for APC function emerged when its association with b-catenin was discovered, providing a molecular link between APC and the Wnt signalling pathway.
The Wnt-signalling cascade is strictly conserved from flies to mammals and controls decisive steps in development and homeostasis of tissues and organs. APC is involved in the regulation of b-catenin at the protein level and the nuclear shuttling of b-catenin.
However, the molecular mechanisms underlying this functions are far from being solved a t present. APC also associates with the plasma membrane at adhesive sites in polarized epithelia. Recent work in mammalian cells and the characterisation of a loss-of-function mutation in Drosophila E-APC suggest novel roles of APC in intercellular adhesion and cell migration.
This proposal combines genetic and biochemical screens to identify most, if not all genes involved in APC function. In particular, we aim to identify APC-binding partners whose binding is abrogated by the (loss-of-function) N175K mutation of E-APC.
This will provide novel insights into the molecular mechanisms underlying this loss-of-function mutation. The thorough characterisation of identified genes will lead to a better understanding of Wnt-signal transduction, but also uncover the variety of APC's cellular functions.
The analysis of APC's role at the plasma membrane and its putative impact on regulating cellular adhesion may have important implications for human malignancies, as they may contribute to tumour progression and metastasis.
Our goal to completely understand the tumour suppressor activity of APC may therefore provide new avenues for therapeutic interventions.
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
- medical and health sciences clinical medicine oncology colorectal cancer
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences zoology mammalogy
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
FP6-2002-MOBILITY-5
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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
LONDON
United Kingdom
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.