The Expression Regulation and Cancer-Promoting Roles of RACGAP1

• Published in: Biomolecules (Basel, Switzerland) Vol. 15; no. 1; p. 3
• Main Authors: Lin, Jiacheng, Zhu, Yuhao, Lin, Zhaoping, Yu, Jindong, Lin, Xiaobing, Lai, Weiyuan, Tong, Beibei, Xu, Liyan, Li, Enmin, Long, Lin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2025; MDPI
• Subjects: Animals; Apoptosis; Bioinformatics; Biomarkers; Breast cancer; Cancer; Cdc42 protein; Cell cycle; Cell division; Cell growth; Colorectal cancer; Cytokinesis; Cytoskeleton; Development and progression; Digestive system; Doxorubicin; ECT2; Gastric cancer; Gene Expression Regulation, Neoplastic; Genetic aspects; Germ cells; GTPase-activating protein; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - metabolism; Guanine nucleotide-binding protein; Humans; Insects; Kinases; Liver cancer; Mediation; Medical prognosis; Molecules; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Nuclear transport; Oncogenes; Oncology, Experimental; Ovarian cancer; Prostate; Proteins; RACGAP1; Respiratory system; Review; Rho-GTPases; rhoA GTP-Binding Protein - genetics; rhoA GTP-Binding Protein - metabolism; RhoA protein; Signal Transduction; STAT3; Stomach cancer; Therapeutic targets; Tumor suppressor genes; Rho-GTPases; RACGAP1; ECT2; STAT3
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom15010003

RACGAP1 is a Rho-GTPase-activating protein originally discovered in male germ cells to inactivate Rac, RhoA and Cdc42 from the GTP-bound form to the GDP-bound form. GAP has traditionally been known as a tumor suppressor. However, studies increasingly suggest that overexpressed RACGAP1 activates Rac and RhoA in multiple cancers to mediate downstream oncogene overexpression by assisting in the nuclear translocation of signaling molecules and to promote cytokinesis by regulating the cytoskeleton or serving as a component of the central spindle. Contradictorily, it was also reported that RACGAP1 in gastric cancer could inactivate Rac and RhoA. In addition, studies have revealed that RACGAP1 can be a biomarker for prognosis, and its role in reducing doxorubicin sensitivity poses difficulties for treatment, while the current drug targets mainly focus on its downstream molecule. This article mainly reviews the expression regulation of RACGAP1 and its cancer-promoting functions through oncogene expression mediation and Rho-GTPase activation.