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 functions as it can also activate Rac and RhoA in multiple cancers. It is involved in various cellular processes such as mediating downstream oncogene overexpression through assisting nuclear translocation of signaling molecules, promoting cytokinesis by regulating the cytoskeleton or being a component of the central spindle. It is associated with multiple signaling pathways including the Hippo, PI3K/AKT, and pathways related to immune cell infiltration [1].

Multiple studies on various cancer types show its significance. In cervical cancer, downregulating RACGAP1 inhibits cell proliferation, migration, and invasion, while overexpressing it has the opposite effects, and it regulates AP-1 via miR-192 and p-JNK [2]. In lung adenocarcinoma, RACGAP1 is overexpressed, promotes cell growth through the PI3K/AKT pathway, and its upregulation is correlated with shorter survival [3]. In breast cancer, RACGAP1 promotes metastasis by regulating mitochondrial quality control, including mitochondrial fission, mitophagy, and biogenesis [4]. In prostate cancer, RACGAP1 promotes neuroendocrine differentiation and enzalutamide resistance, and there is a reciprocal regulation between RACGAP1 and AR contributing to endocrine therapy resistance [5,6].

In conclusion, RACGAP1 plays crucial roles in cancer development and progression across multiple cancer types. It affects processes like cell proliferation, metastasis, and response to therapy. Understanding RACGAP1 through these functional studies can provide potential therapeutic targets for various cancers [2, 4-10].