RACGAP1, a Rho-GTPase-activating protein, was originally discovered in male germ cells. It inactivates Rac, RhoA and Cdc42 from the GTP-bound form to the GDP-bound form. However, it has complex roles in cells as overexpressed RACGAP1 can also activate Rac and RhoA in multiple cancers. It is involved in mediating downstream oncogene overexpression, promoting cytokinesis, and influencing the nuclear translocation of signaling molecules [1].

RACGAP1 is highly expressed across several types of tumors and is associated with a poor prognosis in human cancers. For example, in cervical cancer, downregulating RACGAP1 inhibits cell proliferation, migration, and invasion, while overexpressing it has the opposite effects [2]. In prostate cancer, overexpression of RACGAP1 by E2F1 promotes neuroendocrine transdifferentiation by stabilizing EZH2 expression and also contributes to enzalutamide resistance [3]. In lung adenocarcinoma, RACGAP1 is overexpressed, and its knockdown inhibits cell growth and induces apoptosis through the PI3K/AKT signaling pathway [4].

In conclusion, RACGAP1 plays crucial roles in cancer development and progression, influencing processes such as cell proliferation, metastasis, and cell-cycle progression in various cancers. The studies on RACGAP1 in different cancer types using cell-based and in-vivo models (although specific KO/CKO mouse models are not detailed in the provided references) help understand its functions and nominate it as a potential prognostic biomarker and target for antitumor therapy [1, 2, 4-6].

References:

1. Lin, Jiacheng, Zhu, Yuhao, Lin, Zhaoping, Li, Enmin, Long, Lin. 2024. The Expression Regulation and Cancer-Promoting Roles of RACGAP1. In Biomolecules, 15, . doi:10.3390/biom15010003. https://pubmed.ncbi.nlm.nih.gov/39858398/

2. Zhang, Tianli, Wang, Chunyan, Wang, Kun, Feng, Liping, Yang, Xingsheng. 2022. RacGAP1 promotes the malignant progression of cervical cancer by regulating AP-1 via miR-192 and p-JNK. In Cell death & disease, 13, 604. doi:10.1038/s41419-022-05036-9. https://pubmed.ncbi.nlm.nih.gov/35831303/

3. Song, Zhengshuai, Cao, Qi, Guo, Bin, Ruan, Hailong, Guo, Yonglian. 2023. Overexpression of RACGAP1 by E2F1 Promotes Neuroendocrine Differentiation of Prostate Cancer by Stabilizing EZH2 Expression. In Aging and disease, 14, 1757-1774. doi:10.14336/AD.2023.0202. https://pubmed.ncbi.nlm.nih.gov/37196108/

4. Xu, Zhiyang, Wu, Shaohang, Tu, Jiahua, Guan, Jun, Xu, Jianxin. 2024. RACGAP1 promotes lung cancer cell proliferation through the PI3K/AKT signaling pathway. In Scientific reports, 14, 8694. doi:10.1038/s41598-024-58539-0. https://pubmed.ncbi.nlm.nih.gov/38622149/