Ria Vaishnavi
Research Mentor: Xun Lin
Mentor Department: Surgery, Medicine
Author(s): Ria Vaishnavi, Xun Lin
Session: Session 6 (3:00 PM – 3:50 PM)
Presentation Type: Poster 86
Abstract
Previous findings from the Zou Lab have demonstrated that in Immune Checkpoint Blockades (ICB) CD8+ T cells promote ferroptosis in tumor cells. (Wang et al., 2019) Ferroptosis is an iron-dependent form of cell death. (Ru et al., 2024) Both ferroptosis and iron metabolism are critical in the tumor microenvironment. (Bu & Wang, 2024) Based on these results, we found STEAP2 is a top candidate amongst iron transportation related genes. Overall, patients with lower STEAP2 expression had better clinical outcomes. (Liu et al., 2019) Six Transmembrane Epithelial Antigen of Prostate 2 (STEAP2) is a transmembrane protein belonging to the STEAP family. Our recent work has highlighted STEAP2’s role as a regulator for iron uptake and as a ferroptosis suppressor. In light of these findings, this project aims to identify regulators of STEAP2. Given STEAP2’s abundant expression in prostate tissues and tumors, both of which are rich in hormones, we screened hormones for induction of STEAP2. (Burnell et al., 2018) This revealed that Prednisolone and Hydrocortisone, two corticosteroids that mimic cortisol, induce STEAP2 in both mouse and human cell lines. We optimized conditions for different timepoints (24 hours – 72 hours) and concentrations (0??M – 20??M). We observed dose dependent induction of STEAP2 in RM1 and HT1080 cells. Prednisolone and Hydrocortisone are glucocorticoid receptor (GR) agonists. Consistent with GR signalling regulating the downstream of genes transcriptionally, we observed increased STEAP2 transcripts following optimized treatments with Prednisolone and Hydrocortisone. Based on these observations, we identified that Prednisolone and Hydrocortisone induce STEAP2 expression through transcriptional regulation.
