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  2. Overexpression of KIF2C amplifies tamoxifen resistance and lung metastasis of breast cancer through PLK1/C-Myc pathway

Overexpression of KIF2C amplifies tamoxifen resistance and lung metastasis of breast cancer through PLK1/C-Myc pathway

  • Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar 18. doi: 10.1007/s00210-025-04040-y.
Rui Tian 1 Jilin Kong 1 Hongyan Zang 1 Shuyan Li 1 Xiangjuan Liu 1 Yan Cheng 1 Gaofeng Ni 1 Liguo Gong 2
Affiliations

Affiliations

  • 1 Department of Breast Surgery, Yantaishan Hospital, No. 10087 Keji Road, Laishan District, Yantai, 264000, Shandong, China.
  • 2 Department of Breast Surgery, Yantaishan Hospital, No. 10087 Keji Road, Laishan District, Yantai, 264000, Shandong, China. gongliguo0859@163.com.
Abstract

We highlighted the importance of KIF2C in the development of resistance to tamoxifen and its role in promoting lung metastasis in breast Cancer, as well as the mechanisms that underpin these processes. KIF2C overexpression and knockdown lentiviruses were transfected into MCF-7 and MCF-7/TAM cells. A nude mouse model of MCF-7/TAM tumors and lung metastasis was established. The PLK1 Inhibitor BI2536 was used to explore the underlying mechanism. KIF2C is elevated in tamoxifen-resistant breast Cancer. KIF2C knockdown MCF7/TAM cells show increased sensitivity to tamoxifen, indicated by fewer cell clones, invasive cells, migration area, and lumen count, as well as a higher rate of cell Apoptosis. KIF2C is linked to the PLK1/c-Myc signaling pathway, and BI2536 inhibits its enhancement of tamoxifen resistance. Results from an in situ experiment on breast Cancer in mice are consistent with in vitro findings. KIF2C upregulation is linked to greater tamoxifen resistance in breast Cancer, facilitating progression and lung metastasis in resistant cases. KIF2C's potential mechanism of action is linked to the PLK1/c-Myc signaling pathway.

Keywords

Breast cancer; KIF2C; Lung metastasis; PLK1/c-Myc pathway; Tamoxifen resistance.

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