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Crosstalk signaling between TGF-beta and Wnt/beta-catenin pathways in Adrenocortical Tumors

Grant number: 18/04477-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2018
Effective date (End): August 31, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Carlos Alberto Scrideli
Grantee:Luciana Chain Veronez
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:14/20341-0 - Interactions between emerging therapeutic targets and developmental pathways associated with tumorigenesis: emphasis on pediatric malignancies, AP.TEM

Abstract

Malignant Adrenocortical Tumors (ACT) are rare neoplasms with a significant incidence in children from South and Southeast of Brazil. Advanced stages of these tumors determine aggressive behavior and poor prognosis. Despite decades of study, the Molecular Biology of ACT is still challenging and some well established alterations such activation of Wnt/²-catenin does not confer changes in therapeutic practice. Studies on cancer Molecular Biology expand the observations in the co-participation of many signaling pathways during tumor development and evolution, as well as provide new data for the development of more effective therapies. In the Adrenocortical Tumors context, two pathways can be highlighted: the Wnt/²-catenin, because its contribution for cell survival and the TGF-² pathway, because its dual pro- and anti-tumoral functions. Thus, the aim of this study is to evaluate the influence of the constitutive activation of ²-catenin in the already known interactions between TGF-² and Wnt/²-catenin pathways. For this, it will be performed functional assays with the cell line NCI-H295R after stimulation and blocking of both pathways. In addition, it will be investigated some possible changes in protein interactions and cellular localization of key proteins from both pathways by co-immunoprecipitation and immunofluorescence assays. The existence of interdependent functions between both pathways in Adrenocortical Carcinoma will contribute to a better understanding of the Adrenal Tumors biology and it could determine new study strategies, considering the great complexity of the molecular targets. (AU)