Abstract PS2-11-21: The mechanism research on polyamine targeting ZNF133-L1CAM axis to suppress malignant progression of breast cancer

Abstract Polyamines, which have been found to accumulate in several kinds of body samples in breast cancer patients, are closely related to malignant progression of breast cancer and chemotherapy resistance. However, the downstream molecular mechanism of polyamines is still unclear. We have previously reported that ZNF133 is associated with a favorable prognosis for breast cancer; ZNF133 can inhibit the transcriptional activity of L1CAM gene promoter, inhibit the proliferation and invasion of breast cancer cells in vitro, and inhibit the growth and metastasis of breast cancer in vivo. Polyamines can reduce the level of ZNF133 protein and weaken the inhibitory effect of ZNF133 on the proliferation and invasion of breast cancer cells. Polyamine synthesis inhibitors can increase the level of ZNF133 protein and promote its transcriptional inhibition of L1CAM, thus inhibiting the proliferation and invasion of breast cancer cells. Therefore, we propose a scientific hypothesis: polyamines promote the transcription of L1CAM by inhibiting ZNF133, thus promoting the malignant progression of breast cancer. This project intends to further elaborate the molecular mechanism of polyamine regulation of ZNF133 protein level in breast tumor cells and ZNF133 inhibition of L1CAM transcription, and verify the effect of polyamine metabolism on regulation of ZNF133-L1CAM axis in the malignant progression of breast cancer, providing a new target for the diagnosis and treatment of breast cancer. Citation Format: c. xiao, l. Li, y. Tu, y. Zhu. The mechanism research on polyamine targeting ZNF133-L1CAM axis to suppress malignant progression of breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-11-21.