Arhgap9, also known as Rho GTPase activating protein 9, is a gene that can inactivate Rho GTPases by hydrolyzing GTP into GDP. It is involved in regulating multiple cancer-related cellular events through inhibiting JNK/ERK/p38 and PI3K/AKT signaling pathways, and its genetic/epigenetic variations and abnormal expression are associated with various diseases, especially cancers [1].

In lung adenocarcinoma, knockdown of Arhgap9 promotes cell proliferation, migration, and invasion, inhibits apoptosis, and reduces G0G1 cell cycle arrest by activating the Wnt/β-catenin signaling pathway via suppressing DKK2 [2]. In colorectal cancer, over-expression of Arhgap9 inhibits cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT), while knockdown promotes these processes. Arhgap9 exerts these effects by targeting the PI3K/AKT/mTOR signaling pathway [3]. In hepatocellular carcinoma, Arhgap9 overexpression can inhibit cell proliferation, migration, invasion, and lung metastases through up-regulating FOXJ2/E-cadherin [4]. In gastric cancer, Arhgap9 siRNA inhibits cell viability, migration, invasion, and EMT via inactivating Akt and p38 signaling and inhibiting MMP2 and MMP9 [5]. In bladder cancer, down-regulation of Arhgap9 expression is associated with a poor prognosis [6]. In breast cancer, knockdown of Arhgap9 reduces cell proliferation, migration, and invasive ability, and induces G0-G1 cell cycle arrest and apoptosis [7].

In conclusion, Arhgap9 plays a crucial role in regulating cancer-related cellular processes such as proliferation, apoptosis, migration, invasion, and EMT. Through various loss-of-function experiments in different cancer cell lines, its significance in multiple cancer types has been revealed, highlighting its potential as a biomarker and therapeutic target for cancer treatment.