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Influence of Notch/Nodal signalling pathways cross-talk and microRNAs in thyroid cancer

Grant number: 17/04639-7
Support type:Scholarships in Brazil - Master
Effective date (Start): July 01, 2017
Effective date (End): October 31, 2019
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Edna Teruko Kimura
Grantee:Paola Marino Dantonio
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):18/15868-0 - Modulation of NODAL expression in cancer models in vitro/cell lines, BE.EP.MS

Abstract

Genetic alterations in BRAF, RAS or RET genes are associated to thyroid cancer oncogenesis, being BRAFT1799A (BRAFV600E) mutation the most frequent and associated with greater aggressiveness and poor prognosis. Aggressive thyroid carcinomas show loss of cell differentiation and improved capacity of invasion and migration, due to the activation of epithelial-mesenchymal transition process. Nodal signaling pathway, which is part of the TGF² superfamily, is activated during embryogenesis and is related to stem-cell characteristics, and its reactivation has been demonstrated in several neoplasms. Studies demonstrate that NODAL expression is regulated by Notch signaling pathway, suggesting a cross-talk between these two pathways. Moreover, Notch signaling also play an important role in embryonic phase, and its reactivation has also been reported in cancer. Our group has demonstrated increased NOTCH1 expression in human papillary thyroid carcinoma and BRAF-transgenic mice papillary thyroid cancer, and also that BRAFV600E induces Notch activation, suggesting a relationship between this oncogene and Notch signaling pathway. Furthermore, BRAFV600E mutation induces the expression of microRNAs that negatively modulate the anti-proliferative TGF² signaling pathway. However, the interrelation between Notch/Nodal pathways, modulated by microRNAs, is still underexplored in thyroid cancer. In this extent, we aim to investigate a potential influence of Notch and Nodal signaling pathways and microRNAs in thyroid cancer oncogenesis, and in the acquisition of a more aggressive and less differentiated phenotype. (AU)

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