Targeting kinesin family member 20A sensitizes stem-like triple-negative breast cancer cells to standard chemotherapy
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. KIF20A is essential for triple-negative breast cancer stem cells, and its inhibition suppresses tumor initiation and enhances chemotherapy response, offering a potential treatment strategy.
Authors
- Masashi Takeda (ORCID: https://orcid.org/0000-0001-6673-8399)
- Jun Qun Fang (ORCID: https://orcid.org/0000-0001-9532-8444)
- Chengheng Liao (ORCID: https://orcid.org/0000-0002-9073-3835)
- Lei Guo (ORCID: https://orcid.org/0000-0003-1733-1802)
- Hongwei Yao (ORCID: https://orcid.org/0000-0003-3995-6520)
- ShiNa Li (ORCID: https://orcid.org/0000-0003-0701-9938)
- Weilong Chen (ORCID: https://orcid.org/0000-0001-5843-9073)
- Lianxin Hu (ORCID: https://orcid.org/0000-0001-5600-5634)
- Tuo Wang (ORCID: https://orcid.org/0000-0002-9862-5038)
- Yayoi Adachi (ORCID: https://orcid.org/0000-0002-5134-8854)
- Hao Fu (ORCID: https://orcid.org/0000-0003-0121-0248)
- Jin Zhou (ORCID: https://orcid.org/0000-0001-8121-4198)
- Fei Zhao (ORCID: https://orcid.org/0000-0002-2215-5981)
- Xian Chen (ORCID: https://orcid.org/0000-0002-8358-1247)
- Cheng Zhang (ORCID: https://orcid.org/0000-0001-7665-8675)
- Hongyi Liu (ORCID: https://orcid.org/0000-0003-2081-5779)
- Qing Zhang (ORCID: https://orcid.org/0000-0003-4666-2547)
- Ling Xie
- Lin Xu (ORCID: https://orcid.org/0000-0002-3133-835X)
- Qian Liang (ORCID: https://orcid.org/0000-0003-2083-3491)
- Rachel Shi (ORCID: https://orcid.org/0000-0002-2967-9825)
- Nina Gildor
Institutions
- University of North Carolina at Chapel Hill (US)
Publication Details
- Journal
- UNC Libraries
- Published
- 2025-12-19
- DOI
- https://doi.org/10.17615/wy0f-mf84
- Primary Topic
- Chromatin Remodeling and Cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Texas Southwestern Medical Center
- National Institutes of Health