Objective
Metastasis accounts for 90% of cancer deaths, and it is therefore important and timely to identify new therapeutic targets aimed specifically at metastasis. Cdc42 has recently been implicated in a key step of the metastatic cascade: the extravasation of circulating tumour cells, also termed transendothelial migration (TEM) . This project aims to study how Cdc42 contributes to breast cancer cell TEM in vitro and in vivo. Cdc42 regulates β1‐integrin expression via the transcription factor serum response factor (SRF) and thereby stimulates cancer cell adhesion to endothelial cells (ECs) and TEM. To analyse the molecular basis for this regulation, downstream targets of Cdc42 will be depleted by RNAi in a panel of breast cancer cells to determine which target/s are responsible for altering β1‐integrin expression, adhesion to ECs or TEM.
Cancer cells interact with platelets as soon as they enter the bloodstream, and this enhances cancer cell TEM in vivo. It is therefore possible that Cdc42 regulates attachment to platelets as well as ECs. The role of Cdc42 in the interaction between platelets and cancer cells will be tested by adding purified platelets to control or Cdc42‐depleted breast cancer cells in vitro and analysing platelet aggregation around cancer cells by confocal microscopy. The role of Cdc42 in platelet attachment to cancer cells during early lung colonization in vivo will be studied by intravenous injection of fluorescently tagged breast cancer cells in mice.
This project will increase our understanding of metastasis. The identification of molecular targets involved in cancer cell extravasation will provide a starting point for the development of new drugs, thus contributing to reduce the mortality of patients with metastasis.
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.
- medical and health sciences clinical medicine oncology prostate cancer
- natural sciences biological sciences cell biology
- medical and health sciences clinical medicine oncology breast cancer
- natural sciences physical sciences optics microscopy confocal microscopy
- natural sciences biological sciences genetics RNA
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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.
(opens in new window) H2020-MSCA-IF-2014
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
WC2R 2LS 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.