Zwint-KO 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 [3,6]. It can recruit dynamic protein kinase and dynein, playing a key role in promoting chromosome movement and regulating the spindle assembly checkpoint (SAC), which is crucial for faithful chromosome segregation during cell division [3,8].

Functional studies have shown that Zwint knockdown in various cancer cell lines has significant impacts. In melanoma cells, it suppressed proliferation and migration, and this was associated with decreased expression of c-Myc, MMP-2, Slug, mTOR, p-mTOR, p-p38 and fibronectin, while increasing E-cadherin and MMP-9 expression. 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 cells, Zwint knockdown reduced proliferation, inhibited cell migration, invasion, apoptosis, and colony formation, and also reduced tumor volume in a mice tumor model. Transcriptome sequencing indicated potential related pathways such as TNF, P53, and PI3K [2]. In pancreatic cancer, hypoxia-induced Zwint promoted cancer growth and cell cycle progression by interacting with p53/p21, promoting p53 ubiquitination and degradation [4]. In cervical cancer cells, Zwint promoted proliferation, migration, and invasion by suppressing the p53/p21 signaling pathway [5]. In glioblastoma cells, Zwint knockdown effectively inhibited proliferation and invasion, induced apoptosis, and suppressed tumor growth in vivo [7]. In colorectal cancer, both KIFC1 and Zwint knockdown attenuated spheroid formation ability, and KIFC1 was shown to regulate Zwint [9].

In conclusion, Zwint is crucial for cell division processes through its role in the spindle assembly checkpoint. Research using loss-of-function models, such as knockdown in various cancer cell lines, has revealed its significant role in promoting the progression of multiple cancers, including melanoma, lung, pancreatic, cervical, glioblastoma, and colorectal cancer. These findings suggest that Zwint could be a potential therapeutic target for these cancer types.

References:

1. Mou, Kuanhou, Zhang, Jian, Mu, Xin, Liu, Wenli, Ge, Rui. 2021. Zwint facilitates melanoma progression by promoting c-Myc expression. In Experimental and therapeutic medicine, 22, 818. doi:10.3892/etm.2021.10250. https://pubmed.ncbi.nlm.nih.gov/34131441/

2. Peng, Fang, Li, Qiang, Niu, Shao-Qing, Chen, Ming, Bao, Yong. 2019. ZWINT is the next potential target for lung cancer therapy. In Journal of cancer research and clinical oncology, 145, 661-673. doi:10.1007/s00432-018-2823-1. https://pubmed.ncbi.nlm.nih.gov/30643969/

3. He, Yan, Li, Rui, Gu, Liming, Yu, Shun, Wang, Gefei. 2020. Anaphase-promoting complex/cyclosome-Cdc-20 promotes Zwint-1 degradation. In Cell biochemistry and function, 38, 451-459. doi:10.1002/cbf.3499. https://pubmed.ncbi.nlm.nih.gov/31945194/

4. Chen, Peng, He, Zhiwei, Wang, Jie, Liu, Xinyuan, Jiang, Jianxin. 2021. Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21. In Frontiers in cell and developmental biology, 9, 682131. doi:10.3389/fcell.2021.682131. https://pubmed.ncbi.nlm.nih.gov/34900978/

5. Ma, Zhe, Cai, Yufei, Tian, Chenchen. . ZWINT promotes the proliferation, migration, and invasion of cervical cancer cells by regulating the p53/p21 signaling pathway. In The Chinese journal of physiology, 66, 372-378. doi:10.4103/cjop.CJOP-D-23-00001. https://pubmed.ncbi.nlm.nih.gov/37929349/

6. Lin, Tong, Zhang, Yingzhao, Lin, Zhimei, Peng, Lisheng. 2021. ZWINT is a Promising Therapeutic Biomarker Associated with the Immune Microenvironment of Hepatocellular Carcinoma. In International journal of general medicine, 14, 7487-7501. doi:10.2147/IJGM.S340057. https://pubmed.ncbi.nlm.nih.gov/34744456/

7. Yang, Li, Han, Na, Zhang, Xiaoxi, Chen, Rui, Zhang, Mengxian. 2020. ZWINT: A potential therapeutic biomarker in patients with glioblastoma correlates with cell proliferation and invasion. In Oncology reports, 43, 1831-1844. doi:10.3892/or.2020.7573. https://pubmed.ncbi.nlm.nih.gov/32323832/

8. Woo Seo, Dong, Yeop You, Seung, Chung, Woo-Jae, Kim, Jae-Sung, Su Oh, Jeong. 2015. Zwint-1 is required for spindle assembly checkpoint function and kinetochore-microtubule attachment during oocyte meiosis. In Scientific reports, 5, 15431. doi:10.1038/srep15431. https://pubmed.ncbi.nlm.nih.gov/26486467/

9. Akabane, Shintaro, Oue, Naohide, Sekino, Yohei, Ohdan, Hideki, Yasui, Wataru. 2021. KIFC1 regulates ZWINT to promote tumor progression and spheroid formation in colorectal cancer. In Pathology international, 71, 441-452. doi:10.1111/pin.13098. https://pubmed.ncbi.nlm.nih.gov/33819373/