2. Academic Validation
  3. Targeting Eg5 using Arry520 combats gastric cancer by inducing monopolar spindles

Targeting Eg5 using Arry520 combats gastric cancer by inducing monopolar spindles

  • Gene. 2025 Jul 5:955:149458. doi: 10.1016/j.gene.2025.149458.
Na He 1,  Xinyuan Wei 2,  Ruofei Sun 3,  Gengyuan Zhang 4,  Jie Zhao 5,  Xiangyan Jiang 4,  Bo Long 4,  Zeyuan Yu 4,  Wengui Shi 6,  Zuoyi Jiao 7
Affiliations

Affiliations

  • 1 Department of Oncology, Lanzhou University Second Hospital, Lanzhou, Gansu, China; The Second Clinical Medical College, Lanzhou University, Gansu, China.
  • 2 Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
  • 3 Department of Oncology, Dingxi People's Hospital, Gansu, China.
  • 4 The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, People's Republic of China.
  • 5 Department of Pathology, Gansu Provincial Maternity and Chlid-care Hospital, Lanzhou, Gansu, China.
  • 6 Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, People's Republic of China; Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, People's Republic of China. Electronic address: ery_danwg@lzu.edu.cn.
  • 7 The Second Clinical Medical College, Lanzhou University, Gansu, China; The Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, People's Republic of China; Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, People's Republic of China; Biobank of Tumors from Plateau of Gansu Province, Lanzhou University Second Hospital, Lanzhou, People's Republic of China. Electronic address: jiaozy@lzu.edu.cn.
PMID: 40187619 DOI: 10.1016/j.gene.2025.149458
Abstract

Eg5, also known as KIF11, is a motor protein essential for establishing a bipolar spindle and ensuring proper chromosome congression during Mitosis. It is amplified in various human cancers and serves as a critical oncogene driving tumour progression. However, the role and clinical significance of Eg5 in gastric Cancer has remained elusive. In this study, we showed that Eg5 is upregulation in gastric Cancer tissues and is negatively associated with patient prognosis. The ablation of Eg5 inhibits the proliferation and migration of gastric Cancer cells and suppresses tumour growth in xenograft mice. Mechanistically, Eg5 ablation induces the formation of monopolar spindle, leading to cell Apoptosis and consequent inhibition of tumour growth. Furthermore, Arry520 is demonstrated as a potent Eg5 inhibitor which blocks tumour growth by increasing the formation of cell monopolar spindle and inducing Apoptosis. Arry520 exhibits efficiently therapeutic effects on gastric Cancer in tumour Organoid models, cell-derived xenografts and patient-derived xenografts (PDX) in mice. Collectively, our findings provide evidence for the oncogenic properties of the mitotic protein Eg5 and identify Arry520 as a promising strategy to combat gastric Cancer.

Keywords

Eg5; Eg5 inhibitor; Gastric cancer; Mitotic kinesin protein.

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