TY  - EJOU
AU  - Jeong, Yisun 
AU  - Yang, Sun Moon 
AU  - Yoon, Sun Young 
AU  - You, Ji ng 
AU  - Lee, Eun-Shin 
AU  - Oh, Harim 
AU  - Sim, Jongmin 
AU  - Jung, Seung Pil 
AU  - Kim, Sangmin 
AU  - Lee, Jeong Eon 

TI  - Aberrant Induction of KIF11 Correlates with Unfavorable Outcomes in ER-α Positive Breast Cancer
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - <b>Objectives:</b> Kinesin family member 11 (KIF11), also known as Eg5, is a kinesin motor protein that plays a critical role in mitotic spindle organization and cell division. Although KIF11 has been implicated in promoting cell proliferation and invasive behavior across various cancer types, its regulatory mechanisms in breast cancer remain poorly defined. In this study, we investigated the mechanisms underlying KIF11 regulation and evaluated the therapeutic potential of its selective inhibitor, ispinesib, in breast cancer models. <b>Methods:</b> Prognostic correlations were investigated using clinical cohorts and publicly available datasets. Gene Ex-pression Omnibus (GEO) data were analyzed to examine the relationship between KIF11 and mitogen-activated protein kinase (MAPK) expression. In addition, functional experiments employing genetic modifications and pharmacological inhibitors were conducted in estrogen receptor-positive (ER+) breast cancer cells. <b>Results:</b> High KIF11 expression was significantly linked to inferior survival outcomes in ER+ breast cancer patients and was more frequently observed in those with lymph node-positive (LN+) and advanced-stage disease, supporting its potential contribution to tumor progression. Moreover, KIF11 levels showed a positive association with MAPK1. Pharmacologic blockade of mitogen-activated protein kinase kinase 1/2 (MEK1/2) markedly suppressed KIF11 expression, whereas overexpression of constitutively active MEK1 (CA-MEK1) enhanced its expression, indicating that KIF11 is regulated through MAPK-dependent signaling pathways. Finally, we investigated the impact of the pharmacological inhibitor ispinesib, as well as genetic silencing of KIF11, on cell cycle dynamics and tumor cell proliferation. Both KIF11 knockdown and ispinesib treatment induced gap2/mitosis (G2/M) arrest and substantially curtailed the growth of ER+ breast cancer cells. <b>Conclusion:</b> These findings suggest that KIF11 may serve as a prognostic marker and potential therapeutic target in ER+ breast cancer, and that its expression is, at least in part, modulated through MAPK-dependent signaling pathways.
KW  - Estrogen receptor (ER)-positive breast cancer; prognosis; kinesin family member 11; mitogen-activated protein kinase (MAPK); cell cycle arrest; therapeutic target

DO  - 10.32604/or.2026.075988