Objective
Around 90% of all cancer-related deaths are due to metastasis. Understanding the process of cancer metastasis is therefore of urgent need to develop new treatments. Aberrant expression of the epidermal growth factor receptor (EGFR), or increased availability of its ligands promote tumour survival and metastasis in multiple cancers. As a result, several anti-EGFR therapeutics are in clinical use, but almost all patients will develop resistance against the treatment. Another strategy to treat EGFR driven cancers is to reduce the pool of available EGFR ligands. The crucial enzyme in EGFR ligand release is A Disintegrin And Metalloproteinase (ADAM) 17. I have unpublished data showing that depletion of ADAM17 significantly inhibits colon cancer growth and metastasis in vivo. However, anti-ADAM17 therapies have failed clinically and thus, we urgently need to understand the regulation of ADAM17. Recent discoveries by Dr. Kveiborg’s group, and collaborators showed that the protein phosphatase PP2A binds to ADAM17, and negatively regulates EGFR ligand release, thereby representing the first known negative regulator for ADAM17. Based on these novel findings, I hypothesize that the PP2A-ADAM17-EGFR axis has the ability to control cancer metastasis. To test this hypothesis, I aim to characterize the functional impact of the PP2A-ADAM17 interaction in cancer spread by creating ADAM17 mutants with different PP2A binding properties in colon cancer cells using CRISPR/Cas9 and functionally evaluate these cells in vitro and in zebrafish and mouse models. Moreover, I aim to unravel the molecular mechanisms of the interplay; applying SILAC coupled mass spectrometry and mutagenesis screening, to evaluate the mechanism by which PP2A affects ADAM17, and the signals involved in PP2A binding. This work will pave the way for the development of novel anti-cancer drugs and thereby expand the therapeutic choices for EGFR driven cancers and improve the patient survival.
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 colorectal cancer
- natural sciences chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
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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-EF-ST - Standard EF
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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-2017
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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.
1165 KOBENHAVN
Denmark
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.