Arhgap4, Rho GTPase activating protein 4, is a member of the small GTPases protein family and an important Rho family GTPase-activating protein. It is involved in regulating Rho signaling pathway, which is associated with multiple cellular processes such as cell migration, invasion, and adhesion. It may also play a role in integrin-mediated focal adhesions [4].

In cancer research, Arhgap4 shows diverse effects. In colon cancer, its knockdown inhibits cell migration, invasion, and subcutaneous tumorigenesis, and it promotes metastasis through the TGF-β/Smad signaling pathway, and may be related to T cell exhaustion [1,3]. In acute myeloid leukemia, knockdown of Arhgap4 impairs cell viability, colony formation, and induces apoptosis, and it promotes leukemogenesis by inhibiting DRAM1 signaling [2]. In pancreatic cancer, overexpression of Arhgap4 inhibits cell viability, glucose uptake, lactate release, and the activation of mTOR and HIF-1α signaling pathways related to the Warburg effect, and it regulates cell migration and invasion through the HDAC2/β-catenin signaling pathway [5,6].

In conclusion, Arhgap4 is crucial in regulating multiple cellular functions. Research using gene knockdown (a form of functional study similar to gene knockout in concept) in cancer cell lines has revealed its significant roles in cancer-related biological processes, especially in colon, leukemia, and pancreatic cancers. These findings help to understand the mechanisms of cancer development and may provide potential targets for diagnosis and treatment.

References:

1. Jiang, Shuanghong, Tang, Yong, Wang, Xiaobo, Chen, Xinrui, Wang, Xianfei. 2024. ARHGAP4 promotes colon cancer metastasis through the TGF-β signaling pathway and may be associated with T cell exhaustion. In Biochemical and biophysical research communications, 722, 150172. doi:10.1016/j.bbrc.2024.150172. https://pubmed.ncbi.nlm.nih.gov/38805788/

2. Qi, Yan, Hu, Mengjia, Han, Changhao, Wang, Junping, Zeng, Dongfeng. 2023. ARHGAP4 promotes leukemogenesis in acute myeloid leukemia by inhibiting DRAM1 signaling. In Oncogene, 42, 2547-2557. doi:10.1038/s41388-023-02770-y. https://pubmed.ncbi.nlm.nih.gov/37443303/

3. Fu, Ming-Sheng, Pan, Shu-Xian, Cai, Xun-Quan, Lv, Cui-Ting, Pan, Qin-Cong. 2024. ARHGAP4 Inhibits Proliferation and Growth of SW620 Colon Cancer Cells by Cell Cycle and Differentiation Pathways. In Scientifica, 2024, 5791613. doi:10.1155/2024/5791613. https://pubmed.ncbi.nlm.nih.gov/38938545/

4. Kang, Na, Matsui, Tsubasa S, Liu, Shiyou, Deguchi, Shinji. 2021. ARHGAP4-SEPT2-SEPT9 complex enables both up- and down-modulation of integrin-mediated focal adhesions, cell migration, and invasion. In Molecular biology of the cell, 32, ar28. doi:10.1091/mbc.E21-01-0010. https://pubmed.ncbi.nlm.nih.gov/34524873/

5. Shen, Yehua, Chen, Gang, Zhuang, Liping, Lin, Junhua, Liu, Luming. 2019. ARHGAP4 mediates the Warburg effect in pancreatic cancer through the mTOR and HIF-1α signaling pathways. In OncoTargets and therapy, 12, 5003-5012. doi:10.2147/OTT.S207560. https://pubmed.ncbi.nlm.nih.gov/31303760/

6. Shen, Yehua, Xu, Litao, Ning, Zhouyu, Chen, Hao, Meng, Zhiqiang. . ARHGAP4 regulates the cell migration and invasion of pancreatic cancer by the HDAC2/β-catenin signaling pathway. In Carcinogenesis, 40, 1405-1414. doi:10.1093/carcin/bgz067. https://pubmed.ncbi.nlm.nih.gov/30958531/