Zwint-flox Mouse

Zwint, also known as ZW10 interactor or Zeste White 10-interacting kinetochore protein, is an essential component of the centromere and the mitotic spindle checkpoint. It can recruit dynamic protein kinase and dynein to promote chromosome movement and regulate the spindle assembly checkpoint (SAC), playing a crucial role in cell cycle regulation and chromosome segregation [3,8].

Functional studies, including knockdown experiments in various cancer cell lines, have revealed its significant role in cancer progression. For example, in melanoma cells, Zwint knockdown suppressed cell proliferation and migration, and this was associated with decreased expression of c-Myc, MMP-2, Slug, mTOR, p-mTOR, p-p38 and fibronectin, and increased expression of E-cadherin and MMP-9. Overexpression of c-Myc rescued the effects of Zwint knockdown on melanoma cell proliferation and migration, suggesting Zwint may act as an oncogene in melanoma by regulating c-Myc expression [1]. In lung cancer cell lines, knockdown of Zwint reduced cell proliferation, migration, invasion, apoptosis, and colony formation, and also decreased tumor volume in a mice tumor model. Transcriptome sequencing indicated potential ZWINT-related pathways such as TNF, P53, and PI3K signal networks [2]. Similar results were found in cervical cancer, pancreatic cancer, hepatocellular carcinoma, glioblastoma, and colorectal cancer, where Zwint promoted cell proliferation, migration, invasion or spheroid formation, often through regulating related signaling pathways like p53/p21 [4,5,6,7,9].

In conclusion, Zwint is crucial for spindle assembly checkpoint function and chromosome segregation during cell division. Model-based research, especially knockdown experiments in cancer cell lines, has demonstrated its oncogenic role in multiple cancers, suggesting it could be a potential therapeutic target for these diseases.