Objective
Research objectives and content Thyrotropin (TSH) receptor mediate proliferation of thyroid cells and is implicated in hormone secretion, differentiation and tumorigenesis of these cells. TSH acts through a serpentine receptor which has been shown to couple with the heterotrimeric G-proteins Gs, Gq, Gi, G12 and G13 and to activate two main intracellular effectors: cAMP and the proto-oncogene Ras. Recently, G-protein coupled receptors have been shown to regulate cell morphology, growth, survival and transformation through the activation of specific heterotrimeric G-proteins. Depending on the G-protein coupled, distinct signal transduction pathways can be activated. It has been shown that tyrosine phosphorylation of focal adhesion proteins (paxillin, p130Cas, pl25FAK, src), kinase activity of pl25FAK, src, P13K PKC and activation of Ras family GTP-binding proteins (Ras, Rho, Rac and CDC42) can be stimulated through G-protein coupled receptors. Interestingly, these substrates have been shown to be activated and control critical molecular events in signal transduction pathways involved in the action of integrins, growth factor receptors and oncogenes. With this project we plan to identify new signalling components which can be involved in transduction pathways regulating thyroid cell growth through the activation of TSH receptor. We plan to elucidate the molecular events involved in Ras activation following TSH stimulation. In particular, we aim to examine tyrosine phosphorylation of focal adhesion proteins (paxillin, pl30Cas, Shc, p125FAK, src) in response to TSH and whether these substrates are involved in formation of molecular complexes with signalling and adaptor proteins (Grb2, Crk) following TSH-induced tyrosine phosphorylation. We plan to explore also the role of Rho, PI3K and PKC in TSH receptor signalling and to study the involvement of these signalling proteins in Ras activation and cell proliferation of TSHstimulated thyroid cells. Training Content (objective benefit and expected impact)
This project aims to identify new molecular targets in thyroid tumorigenesis whlch could be of potential use in cancer therapy. The practical experience and scientific knowledge that I have gained during my previous position will help in As a result of this, fresh ideas and technologies will be imported in a less-favoured region of the Community and new scientific collaborations will also be initiated.
Links with industry / industrial relevance (22)
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
- medical and health sciences clinical medicine oncology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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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.
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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
80131 Napoli
Italy
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