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Influence of TGFbeta superfamily and regulatory RNAs on MAPK signaling in thyroid tumorigenesis

Grant number: 16/17129-4
Support Opportunities:Regular Research Grants
Duration: December 01, 2016 - February 28, 2019
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Edna Teruko Kimura
Grantee:Edna Teruko Kimura
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Global incidence of thyroid cancer has increased in the last years, stating this type of cancer as the most common of the endocrine system. Although having a good prognosis, a fraction of thyroid cancers becomes refractory to conventional therapy of radioiodine ablation after thyroid tumor resection due to a more aggressive behavior. Despite the well characterized role for MAPK signaling in thyroid cancer oncogenesis, understanding the molecular mechanism involved in progression is far from being clear. TGF² signaling exerts an important role in this process as it promotes epithelial-to-mesenchymal transition (EMT) and induces cell migration and invasion. Recent studies show the reactivation of embryonic signaling pathways such as Nodal/ Notch and Lin28 as important mechanisms involved in the acquisition of stem-cell like phenotype and more aggressive and invasive behavior. Nodal is a member of TGF² super-family expressed during embriogenesis which cross-talks with Notch signaling. However, the involvement of these signaling pathways in thyroid cancer tumorigenesis remains to be clarified. In this study, we will investigate the role of embryonic signaling pathways of Nodal/ Notch and Lin28 and their interplay with microRNAs in order to better understand the molecular mechanisms of thyroid cancer progression. Moreover, we will investigate the feasibility of modulating these signaling pathways pharmacologically as adjuvant therapy for the treatment of aggressive refractory thyroid cancer. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FUZIWARA, CESAR SEIGI; SAITO, KELLY CRISTINA; LEONI, SUZANA GARCIA; LOGULLO WAITZBERG, ANGELA FLAVIA; KIMURA, EDNA TERUKO. The Highly Expressed FAM83F Protein in Papillary Thyroid Cancer Exerts a Pro-Oncogenic Role in Thyroid Follicular Cells. FRONTIERS IN ENDOCRINOLOGY, v. 10, . (16/17129-4, 13/11019-4, 14/50521-0)
CESAR SEIGI FUZIWARA; KELLY CRISTINA SAITO; EDNA TERUKO KIMURA. Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 63, n. 5, p. 536-544, . (14/50521-0, 16/17129-4)
FUZIWARA, CESAR SEIGI; KIMURA, EDNA TERUKO. MicroRNAs in thyroid development, function and tumorigenesis. Molecular and Cellular Endocrinology, v. 456, n. C, SI, p. 44-50, . (16/17129-4, 13/11019-4, 14/50521-0)

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