Objective
Triple negative breast cancer (TNBC) is the most aggressive and lethal breast cancer subtype, but it lacks expression of the estrogen receptor, the canonical driver of breast cancer development and progression. This indicates that there may be other molecular drivers in this context. The glucocorticoid receptor (GR) is a candidate oncogenic factor in TNBC, that has been shown to support TNBC cell proliferation and metastatic spread. Therefore, GR antagonism may be a viable strategy to attenuate TNBC aggressiveness, however, the precise molecular mechanism of GR action in TNBC cells remains to be determined.
Recent experiments performed in the host laboratory demonstrated that GR activation induced lipid droplet (LD) accumulation, and shifted the balance of the metabolic mTOR signaling complexes, promoting mTORC2 activity, in breast cancer cells. Given that mTORC2 is a regulator of lipid metabolism, and has been implicated in the aggressiveness of TNBC, these observations are compelling and may be linked. Therefore, this project aims to investigate the role of these changes in regulating TNBC metastatic spread, by determining the precise molecular mechanism to explain these effects.
To achieve these aims, I will firstly determine the interactome of the GR-induced mTORC2 and investigate the consequences of these specific interactions in TNBC cells, including on LD accumulation. Subsequently, I will use patient-derived organoids to determine the contribution of the GR-induced LDs to TNBC metastatic capacity and oncogenic phenotypes.
The successful completion of this project will answer key questions relating to the role of GR as an oncogenic factor in TNBC, and define a novel interaction between the GR and mTORC2 signaling axes, which has never been described. In the long term, these findings could facilitate the design and implementation of novel therapeutic options for TNBC, to improve the outcomes for patients diagnosed with this aggressive breast cancer subtype.
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.
You need to log in or register to use this function
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.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
See all projects funded under this funding scheme
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
See all projects funded under this callCoordinator
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.
3584 CX Utrecht
Netherlands
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.