Project description
Molecular players of cancer metastasis
Cancer cells have the remarkable ability to travel through the blood stream or the lymphatic system to distant tissues and cause metastases. Clusters of circulating tumour cells (CTCs) are usually responsible for metastasis formation, but little is known on how their size impacts their metastatic potential. The EU-funded RYTAC project will investigate the dynamics of CTC clusters and especially the role of the YAP and TAZ proteins, transcriptional coactivators with opposing roles in various cellular functions. Researchers will delineate the localisation of these proteins in CTC clusters and its association with metastatic lesions. Project findings will have a significant impact on the clinical management of cancer and the design of targeted treatments.
Objective
Metastasis is the leading cause of all cancer-related deaths. Circulating Tumour Cells (CTCs) are cancer cells that shed off the primary tumour, enter into blood vessels and through the blood circulation are transferred to distant organs, whereby they establish new metastatic lesions. CTCs are detected as single cells and/or clusters of cells with clusters being more metastasis-prone than single CTCs. CTC clusters have different sizes varying from 2- to 50-cells. However, it still remains unknown if the different size of CTCs has an impact on their metastatic potential and what factors regulate their size. To elucidate the molecular dynamics of clustered CTC formation, we performed RNA-seq analysis in cells from primary tumours and CTCs and identified the YAP/TAZ gene signature to be upregulated in CTCs. YAP/TAZ is an interesting molecular node, as its function depends on its subcellular localisation. Junctional localised YAP/TAZ inhibits cancer cell dissemination by supporting the maintenance of cell-cell adhesions, while nuclear YAP/TAZ induces a genetic program that promotes cancer progression. We hypothesised that YAP/TAZ could play a critical role on CTC biology, regulating the size and metastatic potential of CTCs. Thus, the aim of this fellowship is to determine the impact of the size of clustered CTCs on establishing metastatic lesions and provide mechanistic insight on the role of YAP/TAZ. More specifically, I will determine: 1) the localisation of YAP/TAZ in CTCs from mouse models and patients with breast cancer, 2) if YAP/TAZ affects the size of clustered CTCs in breast cancer mouse models, 3) if YAP/TAZ localisation affects the metastatic potential of CTC clusters of variable sizes and 4) signals regulating the nucleocytoplasmic shuttling of YAP/TAZ in CTCs. Hence, this research could be the foundation for developing novel anticancer therapies and an improved patient stratification system.
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.
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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-2020
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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.
8092 Zuerich
Switzerland
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.