Investigating the Mechanism of IFN-γ-Inducible Lysosomal Thiol Reductase-Mediated Inhibition of Breast Cancer Cell Proliferation.

Background: Breast cancer has become a severe threat to human health, making it imperative to identify effective drugs and therapeutic targets. Methods: Various molecular biology experiments, such as western blot analysis, cytologic effect, co-immunoprecipitation, and immunofluorescence assays, as well as a nude mouse xenograft tumor model, were used to comprehensively analyze the impact of gamma-interferon-inducible lysosomal thiol reductase (GILT) on the malignant phenotype of breast cancer cells. This work was performed to examine GILT expression levels and explore the potential mechanism in breast cancer. Results: GILT protein expression levels were significantly lower in breast cancer cells than in normal breast epithelial cells. Overexpressing GILT inhibited breast cancer cell proliferation and migration and slowed tumor growth. GILT inhibited the interaction between the MYC and WDR5 transcription complex and played a tumor-suppressive role. The MYC/WDR5 transcription complex inhibitor OICR-9429 could synergize with GILT to inhibit breast cancer cell proliferation. Conclusion: This study reveals a potential mechanism by which GILT can slow breast cancer growth, as well as identifying the possible clinical application value of small molecule inhibitor OICR-9429. These data collectively provide novel treatment strategies for breast cancer therapy.