Ptpn20, encoding protein tyrosine phosphatase non-receptor type 20, is a non-receptor tyrosine phosphatase. It has been implicated in multiple biological processes. Its catalytic domain shows activity towards tyrosyl phosphorylated substrates, and one of its variants, hPTPN20a, has a dynamic subcellular distribution, targeting to sites of actin polymerization [6]. It may also be involved in pathways related to innate immunity, cell movement regulation, and is part of the PTPN gene family which is associated with protein dephosphorylation [3,4,5].

In triple-negative breast cancer (TNBC), Ptpn20 promotes metastasis by activating NF-κB signaling. It dephosphorylates p65 at Ser468, preventing its binding to COMMD1 and degradation. Downregulation of Ptpn20 inhibits the migratory and invasive abilities of TNBC cells [1]. In H-Tx rats and Ptpn20-knockout (Ptpn20-/-) mice, deletion of Ptpn20 enhances phosphorylation of the NKCC1 cotransporter in the choroid plexus, potentially causing overproduction of cerebrospinal fluid and contributing to hydrocephalus [2].

In summary, Ptpn20 plays critical roles in cancer metastasis and hydrocephalus. Its function in TNBC metastasis through NF-κB signaling activation and its role in hydrocephalus formation via NKCC1 phosphorylation in Ptpn20-/-mice models provide insights into these disease mechanisms, suggesting it could be a potential therapeutic target in both TNBC and hydrocephalus [1,2].

References:

1. Zuo, Xiaoxiao, Zhao, Xiaohan, Zhang, Xiaofei, Shi, Dongni, Qian, Xueke. 2024. PTPN20 promotes metastasis through activating NF-κB signaling in triple-negative breast cancer. In Breast cancer research : BCR, 26, 155. doi:10.1186/s13058-024-01910-w. https://pubmed.ncbi.nlm.nih.gov/39506852/

2. Xu, Hanbing, Miyajima, Masakazu, Nakajima, Madoka, Arai, Hajime, Kondo, Akihide. 2022. Ptpn20 deletion in H-Tx rats enhances phosphorylation of the NKCC1 cotransporter in the choroid plexus: an evidence of genetic risk for hydrocephalus in an experimental study. In Fluids and barriers of the CNS, 19, 39. doi:10.1186/s12987-022-00341-z. https://pubmed.ncbi.nlm.nih.gov/35658898/

3. Ma, Lianjun, Liu, Yang, Wang, Yizhao, Ye, Shujun, Liu, Yanqing. 2023. Identification of PTPN20 as an innate immunity-related gene in gastric cancer with Helicobacter pylori infection. In Frontiers in immunology, 14, 1212692. doi:10.3389/fimmu.2023.1212692. https://pubmed.ncbi.nlm.nih.gov/37359510/

4. van Eekelen, Mark, Runtuwene, Vincent, Masselink, Wouter, den Hertog, Jeroen. 2012. Pair-wise regulation of convergence and extension cell movements by four phosphatases via RhoA. In PloS one, 7, e35913. doi:10.1371/journal.pone.0035913. https://pubmed.ncbi.nlm.nih.gov/22545146/

5. Wang, Fengxu, Wang, Xuehai, Liu, Lei, Zhao, Xinyuan, Gao, Erli. 2022. Comprehensive analysis of PTPN gene family revealing PTPN7 as a novel biomarker for immuno-hot tumors in breast cancer. In Frontiers in genetics, 13, 981603. doi:10.3389/fgene.2022.981603. https://pubmed.ncbi.nlm.nih.gov/36226189/

6. Fodero-Tavoletti, Michelle T, Hardy, Matthew P, Cornell, Brent, Kemp, Bruce E, Tiganis, Tony. . Protein tyrosine phosphatase hPTPN20a is targeted to sites of actin polymerization. In The Biochemical journal, 389, 343-54. doi:. https://pubmed.ncbi.nlm.nih.gov/15790311/