Impact of Depletion or Overexpression on Gene Expression in Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC), known for its aggressiveness and high lethality, presents a significant challenge in terms of treatment. Its heterogeneity and absence of hormone receptors or HER2 expression further limit the availability of targeted therapies. Breast cancer stem cells (BCSCs), recognized for their role in fueling TNBC malignancy, are now being targeted as a vulnerability for TNBC treatment. In this study, we analyzed the transcriptome of BCSCs and identified Kinesin Family Member 20A (KIF20A) as an essential gene for BCSC survival and TNBC tumorigenesis. Depletion or pharmacological inhibition of KIF20A impairs BCSC viability, tumor initiation, and development both in vitro and in vivo. Mechanistically, KIF20A regulates BCSC stemness by modulating the oxidative phosphorylation (OXPHOS) pathway in mitochondria. Our findings underscore the importance of targeting KIF20A as a strategy to exploit BCSC vulnerability in TNBC.