ASAP3, also known as DDEFL1, ACAP4, and UPLC1, is an Arf GTPase-activating protein. It is involved in regulating Arfs by stimulating their intrinsic GTP hydrolysis. ASAP3 is associated with multiple biological activities, including cell migration, invasion, and cytoskeletal remodeling, and is also linked to the NF-κB and NOTCH signaling pathways. Its functions are crucial in normal cell processes and have implications in disease development [4,5].

In conditional knockout (CKO) mouse models, deletion of ASAP3 in parietal cells led to elongation and stacking of microvilli, decreased gastric acid secretion, and active assembly of F-actin due to a higher level of GTP-bound Arf6 GTPase, suggesting its role in regulating microvilli structure and gastric acidity [2]. In cancer research, down-regulation of ASAP3 in various cancer cell lines (such as lung adenocarcinoma, non-small cell lung cancer, and colorectal cancer cells) inhibited cell migration, invasion, and proliferation. For example, in lung adenocarcinoma, ASAP3 overexpression promoted cell migration and tumor progression, and was a downstream target of HIF-1α [1,3,5,6,7].

In summary, ASAP3 is essential for regulating cell movement, cytoskeletal structure, and is involved in disease-related processes such as cancer progression and gastric acidity-associated disorders. The use of CKO mouse models has been instrumental in revealing its role in microvilli structure regulation in parietal cells, while in vitro loss-of-function experiments in cancer cell lines have shown its significance in cancer development, providing potential therapeutic targets for related diseases [2,1,3,5,6,7].

References:

1. Zhang, Pingping, Sun, Junwei, Kai, Jindan, Zhou, Fuxiang, Wu, Jianping. 2019. ASAP3 is a downstream target of HIF-1α and is critical for progression of lung adenocarcinoma. In OncoTargets and therapy, 12, 5793-5803. doi:10.2147/OTT.S199603. https://pubmed.ncbi.nlm.nih.gov/31410024/

2. Qian, Jin, Li, Yueyuan, Yao, Han, Xu, Jie, Fang, Jing-Yuan. 2017. ASAP3 regulates microvilli structure in parietal cells and presents intervention target for gastric acidity. In Signal transduction and targeted therapy, 2, 17003. doi:10.1038/sigtrans.2017.3. https://pubmed.ncbi.nlm.nih.gov/29263912/

3. Fan, Chuifeng, Tian, Yuan, Miao, Yuan, Luan, Lan, Wang, Enhua. . ASAP3 expression in non-small cell lung cancer: association with cancer development and patients' clinical outcome. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 35, 1489-94. doi:. https://pubmed.ncbi.nlm.nih.gov/24078447/

4. Ha, Vi Luan, Bharti, Sanita, Inoue, Hiroki, Ward, Yvona, Randazzo, Paul A. 2008. ASAP3 is a focal adhesion-associated Arf GAP that functions in cell migration and invasion. In The Journal of biological chemistry, 283, 14915-26. doi:10.1074/jbc.M709717200. https://pubmed.ncbi.nlm.nih.gov/18400762/

5. Tian, Haiying, Qian, Jin, Ai, Luoyan, Xu, Jie, Fang, Jing-Yuan. 2017. Upregulation of ASAP3 contributes to colorectal carcinogenesis and indicates poor survival outcome. In Cancer science, 108, 1544-1555. doi:10.1111/cas.13281. https://pubmed.ncbi.nlm.nih.gov/28502111/

6. Guo, Lingchuan, Fu, Jianhong, Sun, Shimei, Guo, Lingling, Wang, Shouli. 2019. MicroRNA-143-3p inhibits colorectal cancer metastases by targeting ITGA6 and ASAP3. In Cancer science, 110, 805-816. doi:10.1111/cas.13910. https://pubmed.ncbi.nlm.nih.gov/30536996/

7. Luo, Yu, Kong, Fang, Wang, Zhen, Wang, Xianyuan, Yang, James Y. 2013. Loss of ASAP3 destabilizes cytoskeletal protein ACTG1 to suppress cancer cell migration. In Molecular medicine reports, 9, 387-94. doi:10.3892/mmr.2013.1831. https://pubmed.ncbi.nlm.nih.gov/24284654/