Project description
Insight into the ability of cancer cells to divide in challenging microenvironments
Mammalian cells must round up to divide, providing the space to develop a mitotic spindle for symmetric chromosomal segregation. If mitotic rounding is impeded by physical confinement or malfunction in adhesion remodelling, mitotic cell death may ensue. The EU-funded IEOCCD project aims to identify the mechanisms that allow epithelial cancer cells to divide in a challenging physical environment. Ras-activated epithelial cells are able to round better compared to normal cells, suggesting that Ras-ERK signalling plays a role in the mitotic rounding of cancer cells. The project will study a connection between Ras-ERK signalling and mitotic progression, linking oncogenesis to the ability of cancer cells to divide in a wide range of environments.
Objective
Mammalian cells must round up to divide by remodeling their adhesions and their cytoskeleton to form a stiff actin cortex. Mitotic rounding provides the space necessary to develop a mitotic spindle to undergo symmetric chromosomal segregation. If mitotic rounding is impeded by physical confinement or preventing adhesion remodeling, defects in spindle assembly and chromosomal missegregation can lead to mitotic cell death. In cancer, the cells must divide in a challenging environment which can alter the way cells divide. Preliminary data show Ras- activated epithelial cells are able to round better compared to normal cells. This adaptation could protect the dividing cell from the physical environment and allow epithelial cancer cells to divide in the confines of the tumor and distant metastatic sites. Here, we aim to identify mechanisms that allow epithelial cancer cells to divide differently from that of normal epithelial cells. Potentially, this mechanism could be a powerful target if we are able to prevent cancer cell division without interfering with normal cell division. Preliminary data suggest Ras-ERK signalling could play a role in mitotic rounding of cancer cells. In this proposal, I will 1) investigate ERK signalling dynamics during mitotic progression, how it regulates mitotic rounding and effects on the following cell cycle 2) investigate how Ras-ERK signalling and the mechanism of cell division are affected by environment using microfabricated tools and 3) initiate oncogenic activation by over-expressing receptor tyrosine kinases commonly found over-expressed in cancer or constitutive activation of Ras/Raf and measure changes in Ras-ERK signalling and cell mechanics. By establishing a link between Ras-ERK signalling and mitotic progression, I will determine how oncogenesis affects Ras-ERK signalling dynamics and cell division to allow cancer cells to divide in a wide range of environments.
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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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-2018
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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.
WC1E 6BT 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.