Objective
Breast cancer affects 1 in 8 women and is the chief cause of female cancer
deaths in the EU. Early detection continues to improve survival, but prognosis
worsens significantly after metastasis. Metastasis and chemoresistance are linked
phenomena, but the molecular basis is unknown. The evidence suggests a role for
Caveolin1 (Cav1): i) Cav1 mediates biomechanical remodelling of the extracellular
matrix by cancer-associated fibroblasts (CAFs), promoting invasion (host lab
publications); ii) Cav1 is involved in drug/radiation resistance, and the Cav1β isoform
might regulate resistance of breast tumour cells (TCs) to paclitaxel (literature); iii)
The Cav1 content of breast-TC exosomes correlates with metastatic potential (our
preliminary data).
We propose that acquisition of invasiveness by TCs is related to their release
of Cav1-containing exosomes. Cav1-activated CAFs then increase matrix stiffness,
providing the appropriate milieu for TC metastasis. The N-terminally curtailed Cav1β
precludes chemotherapy-induced tyr14 phosphorylation, preventing Bcl2 binding and
conferring resistance. Cav1 α and β might thus balance the interplay between TCs
and CAFs during tumour progression.
To integrate these data and verify our hypothesis, we propose state-of-the-art approaches and
multidisciplinary strategies, ranging from cell biology to animal
models and clinical screening studies. As side products, tools of interest will be
produced such as a new antibody to Cav1β, useful for stratifying patients according
to their likely benefit from paclitaxel therapy, and a new Cav-/- mouse generated by
ZFN targeting in the NSG strain, which promises a method for conducting human
transplants in genetically modified animal models.
The complementary expertise of fellow and host lab, coupled with the
excellent scientific environment at the host institute, provide a firm basis for success
of this ambitious but sound proposal, thus fostering the fellow’s progress to
independence.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences cell biology
- medical and health sciences clinical medicine oncology breast cancer
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
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.
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.
FP7-PEOPLE-2013-IEF
See other projects for this call
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.
Coordinator
28029 Madrid
Spain
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.