Objective
TGF-ss signalling pathways play an important role in embryonic development as well as intumouri genesis. TGF-ss signalling results in nuclear accumulation of active Smads complexes that regulate transcription of target genes. Alteration of certain TGF-ss pathway components is a frequent event in some human tumours such as colorectal or pancreatic tumours and mainly results from mutation or deletion of either the TGF-ss type II receptor or the Smad4 genes. More frequently however, human tumours tend to express lo w levels of either the type I or type II TGF-ss receptors.
The mechanism by which the TGF-ss pathway contributes to tumour progression is unclear, but it is now known that it can act both as a tumour suppressor by inhibition of growth or as a tumour promoter by increasing motility and inducing epithelial to mesenchymal transition (EMT), invasiveness and metastasis. My project aims to understand how alteration of TGF-ss pathway components in tumours could explain how tumour cells become resistant to the growth in hibitory effects of TGF-ss, whilst maintaining responsiveness to the pro-oncogenic activities of TGF-ss. To assess this question, I will use inducible siRNA technology to generate human pancreatic cell lines that are specifically knocked-down for Smad4 or the type I TGF-ss receptor.
The functional responsiveness of these cell lines to TGF-ss will be investigated by cell cycle analysis and migration assays and I will attempt to determine whether these cells have acquired a more aggressive phenotype by measuring their tumour igenicity. These results will be complemented with micro array analyses in order to determine which target genes are implicated in these different responses.
Finally, using biochemical approaches in the inducible Smad4-siRNA pancreatic cell lines, I will seek to determine why the loss of Smad4 is particularly advantageous for pancreatic tumour progression.
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 developmental biology
- natural sciences biological sciences genetics mutation
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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.