Interaction between estrogen receptors, EGFR and Filamin A in lineages Castration-resistant prostate cancer cells and spheroids

• Grant number: 24/10986-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Carolina Meloni Vicente
• Grantee: Deborah Simão de Souza
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Prostate cancer initially responds well to androgen deprivation therapies, but some tumors can progress to an androgen-independent phenotype, also known as castration-resistant prostate cancer (CRPC), leading to metastasis. The molecular mechanisms that lead to the development of CRPC are not clear. Our laboratory has shown the expression and the extranuclear localization of the estrogen receptors (ERs) ESR1 (ER±) and ESR2 (ER²) in androgen-independent prostate cancer lines DU-145 and PC-3, used as models of CRPC. Furthermore, they demonstrated the importance of estrogen and its receptors in inducing cell proliferation, migration, invasion and rapid signaling pathways related to cancer. Preliminary results from our laboratory also highlighted the interaction between estrogen receptors and the epidermal growth factor receptor (EGFR), through transactivation between receptors. Recently, using 3D cell culture with cocultures of fibroblasts and prostate cancer cells, it was shown that the Filamin A/androgen receptor (AR) complex affects progression and metastasis in prostate cancer, in addition to controlling cell motility and invasiveness. Furthermore, cell culture studies in monolayers indicated that Filamin A regulates cellular signaling pathways activated by EGFR. However, interactions between ERs, EGFR and Filamin A have not yet been described in CRPC, either in cell cultures in monolayers or in spheroids. Thus, the aim of this project is to analyze the function of Filamin A in CRPC, as well as its interaction with ERs and EGFR in these cell cultures.