Project description
Mitochondria’s role in cancer cell invasion
The spread of cancer cells to distant organs from the original site remains the principal reason for cancer deaths. While mesenchymal-like cells are infamous for their invasive properties, it is amoeboid-type cells that are more aptly suited for metastasis. However, the biological switch between the two cell types, or the mesenchymal-to-amoeboid transition (MAT), remains little understood. Supported by the Marie Skłodowska-Curie Actions programme, the MitoMat project investigates how mitochondria are implicated in this process. Using microfluidic, optogenetic and proteomic technologies in combination, the project will shed light on how mitochondria assist in sustaining tumour cell movement and in melanoma. This kind of research holds the potential for the generation of new metastasis-directed therapies.
Objective
Tumor cell migration and invasion represent the foundation of cancer metastasis. It is therefore critical to better understand the
mechanisms driving a specific subset of tumor cells to invade nearby tissues. Invasive cells are known to have an undifferentiated,
mesenchymal-like state. However, under specific microenvironment conditions, mesenchymal cells become amoeboid, through a
process known as the mesenchymal-to-amoeboid transition (MAT). Paradoxically, it is not the mesenchymal cells that are more
metastatic-prone, but the amoeboid cells. What is not yet fully understood is the precise cellular mechanisms driving MAT. Emerging
evidence show that mitochondria are closely linked with cellular motility, especially in cancer. Mitochondrial dynamics, consisting
mainly in mitochondrial fusion, fission, intracellular trafficking and turnover, was proven to be involved in the migration of
mesenchymal-like tumor cells. However, very little is known about the characteristics of lamellipodia-localized mitochondria in these
cancer cells on one hand, and how it might influence MAT and the amoeboid phenotype on the other. Therefore, I first aim to
evaluate the role of mitochondrial dynamics in tumor microenvironment-triggered MAT during the 3D invasion of melanoma cells by
combining microfluidic and optogenetic approaches. Secondly, I will characterize the lamellipodia-localized mitochondria in terms of
proteome, age, energetic and oxidative status, in mesenchymal-like melanoma cells using biochemical, microfluidic and proteomic
approaches. By the end of the project, MitoMat would significantly improve the mechanistic understanding of how mitochondria are
hijacked to fuel cancer cell motility, specifically within melanoma cells with different MAT phenotypes. If mitochondrial dynamics
would prove to be a driver for both cell invasion modalities (mesenchymal and amoeboid), our results could represent the premises
for a future migrastatic therapy, targeting cancer 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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine oncology skin cancer melanoma
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2024-PF-01
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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.
75654 PARIS
France
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.