UFHCC Research Day Poster Award 2023

UFHCC Research Day Poster
Lei Wang

Title: Degrading Nuclear Receptor NR4A1 by Proteolysis-Targeting Chimeras for Cancer Therapy

Abstract: Cellular genes and proteins change during tumor microenvironment (TME) formation. Some proteins overexpression in cancer cells and certain tumor-infiltrating immune cells causes immune suppression in TME and is correlated with poor prognosis. Ideally, we can simultaneously inhibit cancer cell growth and enhance the immune system in cancer treatment by targeting specific proteins. Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) plays a crucial role in cancer development. NR4A1 is overexpressed in cancer cells and related to breast and lung cancer metastasis and invasion. NR4A1 is overexpressed in tumor-infiltrating regulatory T (TI-Treg) cells and exhausted CD8 T cells to suppress the immunity in TME. Here, we developed NR4A1 degraders by using the Proteolysis-Targeting Chimera (PROTAC) strategy, which can efficiently degrade NR4A1 by ubiquitination-proteasome pathway. Our results showed that the NR4A1 PROTCs (NR4A1-Ps) is a safe compound, and it can effectively repress tumor growth and strengthen the anti-tumor immunity.