Ptpn18, protein tyrosine phosphatase nonreceptor type 18, is a member of the protein tyrosine phosphatases (PTP) family. It has been associated with multiple signaling pathways, such as the PI3K/AKT, MYC-CDK4, and EPOR/JAK2 signaling pathways, and plays important roles in various biological processes related to cell growth, survival, and metastasis [1,2,8]. Genetic models, like gene knockout (KO) mouse models, are valuable tools to study its functions.

In cancer research, Ptpn18 shows diverse roles. In ovarian cancer, knockdown of Ptpn18 inhibited the proliferative and migratory abilities of cancer cells, suppressing ovarian cancer growth in nude mice, indicating its potential as an oncogene in ovarian cancer [1]. In colorectal cancer, Ptpn18 overexpression promoted growth and tumorigenesis, while its deficiency had the opposite effect both in vitro and in vivo, and it activated the MYC-CDK4 axis [2]. In glioblastoma, high expression of Ptpn18 correlated with immune suppression and facilitated tumor progression [3]. In contrast, in breast cancer, Ptpn18 was downregulated in metastatic tissues, and its ectopic expression inhibited breast cancer cell metastasis [4]. In hepatocellular carcinoma, Ptpn18 expression was downregulated, and it exerted inhibitory effects on cell proliferation, migration, and invasion, while promoting apoptosis [5]. In endometrial cancer, silencing of Ptpn18 induced ferroptosis, inhibited proliferation and metastasis, and promoted apoptosis [6,7].

In conclusion, Ptpn18 has context-dependent functions in different biological processes and disease conditions, especially in various cancers. Studies using KO or other loss-of-function models have revealed its complex roles in promoting or inhibiting cancer cell growth, metastasis, and other malignant behaviors, which may provide potential diagnostic and therapeutic targets for related diseases.

References:

1. Mao, Nan, Li, Hu, Yang, Hui, Liang, Zhimin, He, Guansheng. 2022. PTPN18 Stimulates the Development of Ovarian Cancer by Activating the PI3K/AKT Signaling. In Evidence-based complementary and alternative medicine : eCAM, 2022, 1091042. doi:10.1155/2022/1091042. https://pubmed.ncbi.nlm.nih.gov/35310041/

2. Li, Chao, Li, Shang-Ze, Huang, Xi-Cheng, Song, Xue-Min, Du, Run-Lei. 2020. PTPN18 promotes colorectal cancer progression by regulating the c-MYC-CDK4 axis. In Genes & diseases, 8, 838-848. doi:10.1016/j.gendis.2020.08.001. https://pubmed.ncbi.nlm.nih.gov/34522712/

3. Wang, Tao, Yu, Yang, Ba, Xinlei, Zhao, Yanjiao, Wang, Bing. 2023. PTPN18 Serves as a Potential Oncogene for Glioblastoma by Enhancing Immune Suppression. In Oxidative medicine and cellular longevity, 2023, 2994316. doi:10.1155/2023/2994316. https://pubmed.ncbi.nlm.nih.gov/36846716/

4. Wang, Tao, Ba, Xinlei, Zhang, Xiaonan, Yu, Yang, Wang, Bing. 2022. Nuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2. In Cell death & disease, 13, 720. doi:10.1038/s41419-022-05167-z. https://pubmed.ncbi.nlm.nih.gov/35982039/

5. Zhou, Zhenyu, Yu, Wei, Li, Huoming, Xiao, Zhiyu, Zhang, Jianlong. . Hepatitis B Virus X Protein Represses Expression of Tumor Suppressor PTPN18 in Hepatocellular Carcinoma. In Molecular cancer research : MCR, 22, 891-901. doi:10.1158/1541-7786.MCR-23-0696. https://pubmed.ncbi.nlm.nih.gov/38787319/

6. Wang, Haibo, Peng, Siyuan, Cai, Junhong, Bao, Shan. 2021. Silencing of PTPN18 Induced Ferroptosis in Endometrial Cancer Cells Through p-P38-Mediated GPX4/xCT Down-Regulation. In Cancer management and research, 13, 1757-1765. doi:10.2147/CMAR.S278728. https://pubmed.ncbi.nlm.nih.gov/33642877/

7. Cai, Junhong, Huang, Sizhe, Yi, Yuping, Bao, Shan. 2019. Downregulation of PTPN18 can inhibit proliferation and metastasis and promote apoptosis of endometrial cancer. In Clinical and experimental pharmacology & physiology, 46, 734-742. doi:10.1111/1440-1681.13098. https://pubmed.ncbi.nlm.nih.gov/31034093/

8. Held, Matthew A, Greenfest-Allen, Emily, Su, Su, Stokes, Matthew P, Wojchowski, Don M. 2020. Phospho-PTM proteomic discovery of novel EPO- modulated kinases and phosphatases, including PTPN18 as a positive regulator of EPOR/JAK2 Signaling. In Cellular signalling, 69, 109554. doi:10.1016/j.cellsig.2020.109554. https://pubmed.ncbi.nlm.nih.gov/32027948/