Targeting Kinesin Family Member 20A Sensitizes Stem-Like Triple-Negative Breast Cancer Cells to Standard Chemotherapy

Authors

Yayoi Adachi
Weilong Chen
Cheng Zhang
Tao Wang
Nina Gildor
Rachel Shi
Haoyong Fu
Masashi Takeda
Qian Liang
Fangzhou Zhao
Hongyi Liu
Jun Fang
Jin Zhou
Hongwei Yao
Lianxin Hu
Shina Li
Lei Guo
Lin Xu
Ling Xie
Xian Chen
Chengheng Liao
Qing Zhang

Publication Date

12-15-2025

Journal

Journal of Clinical Investigation

DOI

10.1172/JCI182394

PMID

41392981

PMCID

PMC12700555

PubMedCentral® Posted Date

12-15-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Triple-negative breast cancer (TNBC), being both aggressive and highly lethal, poses a major clinical challenge in terms of treatment. Its heterogeneity and lack of hormone receptors or HER2 expression further restrict the availability of targeted therapy. Breast cancer stem cells (BCSCs), known to fuel TNBC malignancy, are now being exploited as a vulnerability for TNBC treatment. Here, we dissected the transcriptome of BCSCs and identified kinesin family member 20A (KIF20A) as a key regulator of BCSC survival and TNBC tumorigenesis. Genetic depletion or pharmacological inhibition of KIF20A impairs BCSC viability and tumor initiation and development in vitro and in vivo. Mechanistically, KIF20A supports BCSC stemness through modulation of mitochondrial oxidative phosphorylation, which is repressed by SMARCA4, a component of the SWI/SNF chromatin remodeling complex. Therapeutically, KIF20A inhibition sensitizes TNBC xenografts to standard-of-care chemotherapy. Our study highlights the importance of targeting KIF20A to exploit BCSC vulnerabilities in TNBC.

Keywords

Triple Negative Breast Neoplasms, Kinesins, Humans, Female, Neoplastic Stem Cells, Animals, Mice, Cell Line, Tumor, Xenograft Model Antitumor Assays, Neoplasm Proteins, Transcription Factors, Cell biology, Oncology, Breast cancer, Stem Cells

Published Open-Access

yes

Recommended Citation

Adachi, Yayoi; Chen, Weilong; Zhang, Cheng; et al., "Targeting Kinesin Family Member 20A Sensitizes Stem-Like Triple-Negative Breast Cancer Cells to Standard Chemotherapy" (2025). Faculty, Staff and Student Publications. 6751.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6751