Breast cancer (BC) is the most frequently diagnosed cancer worldwide, with an ever-increasing incidence rate. While screening and treatment methods have improved markedly over the last three decades, BC remains the leading cause of malignant death in women annually. Therefore, there is an urgent need to identify new biomarkers and therapeutic targets for BC. Recently, dysregulated gasdermin D (GSDMD), a central player of inflammation-induced cell death called pyroptosis, has been shown to be implicated in cancer. However, it is unclear whether GSDMD plays important roles in BC. In addition, the molecular mechanism underlying GSDMD-involved tumorigenesis remains unknown. Here, we discovered that GSDMD is significantly upregulated in BC. We have shown that overexpression or knockout of GSDMD increases or decreases BC cell proliferation, respectively. In addition, we have identified and validated several novel GSDMD-interacting proteins that play important roles in breast cancer. These present findings will not only shed light on the roles of GSDMD in BC tumorigenesis but also provide new preclinical data for future successful treatments of BC patients.

Citation Format: Derek Yisen Zhang. Exploring the roles of GSDMD in mammary tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 339.