The function of SWI/SNF Complex DPF paralogues in renal cancer

• Grant number: 24/22126-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: May 05, 2025
• End date: May 04, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Leandro Machado Colli
• Grantee: Leticia Andrade Costa
• Supervisor: Cigall Kadoch
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Dana-Farber Cancer Institute, United States
• Associated to the scholarship: 21/14853-1 - DPF3 Impact on Renal Cancer: from susceptibility to murine treatment with immunotherapy, BP.DD

Abstract

Renal carcinoma (RCC) is one of the ten most frequent types of cancer, with an increasing number of new cases. Clear Cell Renal Carcinoma (ccRCC) is the most frequent subtype, responsible for about 75% of the cases. The SWI/SNF Complex acts in chromatin remodeling, modulating the expression of several genes involved in cell proliferation and immune response. SWI/SNF Complex is composed of several proteins that can organized in several different ways. The DPF3 and DPF2 are paralogues members of the SWI/SNF Complex that are part of the region binding to DNA regions. In vitro studies demonstrated that DPF3 overexpression increased cell growth rates and altered chromatin accessibility in ccRCC, changing gene expression to oncogenic pathways. Other studies show that mice DPF2 knockout increases hematopoietic stem cell differentiation and chronic inflammation, favoring the oncogenic pathways. However, no study has evaluated the interaction between these two paralogue proteins and the regulation of complex assembly for selecting one over the other. Thus, this project aims to evaluate and compare the function of DPF2 and DPF3 in the development of RCC through the BAF Complex. We will develop DPF2 and DPF3 knockout RCC cell lines and analyze the BAF Complex formation with proliferative assays to study the difference between the two proteins in RCC cell line proliferation. We also will combine the DPF3 knockout with DPF2 overexpression to induce the SWI/SNF Complex assembly with DPF2 and analyze the effects of DPF2 overexpression in RCC development. We will isolate the SWI/SNF complex of primary renal cancer cell lines and correlate the preference for DPF2 or DPF3 in the SWI/SNF Complex with the effect of each one in RCC development. This study will be critical for a better understanding of the function of the SWI/SNF Complex in RCC and the participation of DPF2 and DPF3 in developing the disease. This study will be critical for better understanding the function of those DPF paralogues on the very important SWI/SNF Complex, using RCC as a model. Advancing the knowledge of the DPF paralogs may have a future impact on clinical care due to the importance of the SWI/SNF complex in cancer.