Abstract PS4-03-06: Aberrant KIF11 induction is a potential driver of aggressiveness in ER-a positive positive breast cancer

Abstract Kinesin family member 11 (KIF11), also known as Eg5, is a motor protein critical for mitotic spindle formation and proper cell division. While KIF11 has been implicated in promoting cell proliferation and invasion in various cancer types, its regulatory mechanisms in breast cancer remain poorly understood. In this study, we investigated the regulation of KIF11 expression and assessed the therapeutic potential of its specific inhibitor, ispinesib, in breast cancer models. Analysis of the GSE4922 dataset revealed that estrogen receptor-positive (ER+) breast cancer patients with high KIF11 expression exhibited significantly poorer survival compared to those with low expression. Moreover, KIF11 levels were elevated in lymph node-positive (LN+) patients and those with advanced-stage disease, suggesting its potential role in tumor progression. We further found that KIF11 expression was positively correlated with MAPK1 expression and negatively correlated with STAT3 expression. Pharmacological inhibition of MEK1/2 using binimetinib significantly reduced KIF11 expression, whereas overexpression of constitutively active MEK1 (CA-MEK1) increased its expression. KIF11 knockdown (KD) also induced G2/M phase arrest and inhibited cell growth in MCF7 breast cancer cells. Finally, we evaluated the pharmacological efficacy of ispinesib in regulating the cell cycle and cell growth. As expected, ispinesib induced G2/M phase arrest and completely inhibited cell growth in ER+ breast cancer cells. These findings support KIF11 as a prognostic marker and potential therapeutic target in ER+ breast cancer, regulated at least in part by the MAPK signaling pathway. Citation Format: S. Jung, J. Yisun, S. Yang, Y. Sun Young, Y. Ji Young, L. Eun-Shin, O. Harim, S. Jongmin, K. Sangmin, L. Jeong Eon. Aberrant KIF11 induction is a potential driver of aggressiveness in ER-a positive positive 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 PS4-03-06.