Rcc2, also known as TD-60, is a member of the RCC1 family and a telophase disk-binding protein involved in mitosis. It plays a crucial role in ensuring proper cell division, especially cytokinesis, and is associated with multiple signaling pathways, such as Wnt, Hh/GLI1, and JAK-STAT [2,4,5]. Dysregulation of Rcc2 has significant implications for various biological processes and disease development, especially cancer [1-6]. Genetic models, including KO/CKO mouse models, are valuable tools for studying its functions.

In breast cancer, inhibiting Rcc2 expression in MCF-7 cells decreased cell migration, stimulated apoptosis, and reduced tumor growth in mouse models, with associated decreases in genes like IGF1 and TWIST1 [1]. In prostate cancer, Rcc2 knockdown suppressed cell proliferation, migration, invasion, and EMT in vitro, and tumor growth in vivo, through the Hh/Gli1 signaling pathway [2]. In glioblastoma, shRNA-mediated inhibition of Rcc2 showed its essential role in tumor proliferation, tumorigenicity, and radio-resistance in vitro and in vivo, with implications for DNA mismatch repair and DNMT1 activation [3]. In esophageal cancer, Rcc2 deletion in conditional knockout mice decreased tumor nodule formation and progression in the esophagus [6].

In summary, Rcc2 is vital for normal cell division and its dysregulation contributes to cancer development. Studies using KO/CKO mouse models have been instrumental in revealing its role in breast, prostate, glioblastoma, and esophageal cancers, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Wang, Weiqi, Xu, Bing, Zhang, Zhaoxu, Fang, Kehua, Chang, Xiaotian. 2020. RCC2 Expression Stimulates ER-Positive Breast Tumorigenesis. In Journal of oncology, 2020, 5619462. doi:10.1155/2020/5619462. https://pubmed.ncbi.nlm.nih.gov/32565805/

2. Wang, Shenghan, Lei, Zhentao, Liu, Wei, Le, Kai, Zhang, Bao. 2023. RCC2 promotes prostate cancer cell proliferation and migration through Hh/GLI1 signaling pathway and cancer stem-like cells. In Biology direct, 18, 80. doi:10.1186/s13062-023-00439-w. https://pubmed.ncbi.nlm.nih.gov/38008751/

3. Yu, Hai, Zhang, Suojun, Ibrahim, Ahmed N, Deng, Zhong, Wang, Maode. 2019. RCC2 promotes proliferation and radio-resistance in glioblastoma via activating transcription of DNMT1. In Biochemical and biophysical research communications, 516, 999-1006. doi:10.1016/j.bbrc.2019.06.097. https://pubmed.ncbi.nlm.nih.gov/31277942/

4. Xu, Xiaoyang, Huang, Yuliang, Yang, Feng, Xie, Shanshan, Yang, Yuehong. . NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody. In Protein & cell, 15, 766-782. doi:10.1093/procel/pwae025. https://pubmed.ncbi.nlm.nih.gov/38801297/

5. Chen, Zhen, Wu, Wenjing, Huang, Yongsheng, Yin, Dong, Hu, Kaishun. 2019. RCC2 promotes breast cancer progression through regulation of Wnt signaling and inducing EMT. In Journal of Cancer, 10, 6837-6847. doi:10.7150/jca.36430. https://pubmed.ncbi.nlm.nih.gov/31839818/

6. Calderon-Aparicio, Ali, Yamamoto, Hiroyuki, De Vitto, Humberto, Bode, Ann M, Dong, Zigang. 2020. RCC2 Promotes Esophageal Cancer Growth by Regulating Activity and Expression of the Sox2 Transcription Factor. In Molecular cancer research : MCR, 18, 1660-1674. doi:10.1158/1541-7786.MCR-19-1152. https://pubmed.ncbi.nlm.nih.gov/32801160/