Objective
Tumors contain multiple subpopulations of cells some of which may contribute to therapeutic resistance. Moreover phenotypic states in cancer (stem-like; invasive; proliferative; and differentiated) are dynamic and reversible, yet use many of the same signaling pathways implicated in activation and self-renewal of physiological stem cells. Of these, the Wnt/b-catenin signaling pathway plays a major role in stem cell activation and differentiation, and is frequently constitutively activated in cancers. My preliminary results indicate that surprisingly, oleic acid can substitute for Wnt in activation of b-catenin signaling. Adipocytes can play a key role in stem cell activation, can transfer lipids to cancer cells, and are frequently encountered during cancer cell invasion. I hypothesize that lipid uptake by cancer cells will alter metabolism and drive phenotype-switching via b-catenin signaling. This project therefore aims to investigate the biological and metabolic consequences of lipid uptake by cancer cells and will use melanoma as a model system since the key regulators of phenotype-switching in this cancer are known to be targeted by b-catenin signaling. Specifically, I will use standard cell biology techniques to identify the repertoire of lipids able to trigger nuclear localization of b-catenin and the biological consequences of lipid uptake (invasiveness; proliferation; differentiation etc); integrative genomics (ChIP-seq and RNA-seq) to identify direct b-catenin target genes and their relationship to those targeted by the master regulator of the melanocyte lineage, MITF, that is known to interact directly with b-catenin; and metabolomics to identify how lipid uptake and de-regulation of b-catenin signaling affect cellular metabolism. The results will provide a key insight into how lipid signalling can impact on cancer biology and potentially activate physiological stem cells, as well as provide high-level training in emerging technologies.
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 genetics
- medical and health sciences clinical medicine oncology skin cancer melanoma
- natural sciences biological sciences cell biology
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences medical biotechnology cells technologies stem cells
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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.
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
OX1 2JD Oxford
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.