PTPN18 functions as a tumor suppressor in breast cancer by negatively regulating cyclin E

作者：Na Zhang, Tao Wang, Bin Bai, Xiaonan Zhang, Wenying Xu, Weilu Chen, Yang Yu, Bing Wang · 发表于：International Journal of Oncology · 年份：2025 · DOI：10.3892/ijo.2025.5843 · 被引用次数：1 · 研究领域：Protein Tyrosine Phosphatases、Diabetes and associated disorders、Glycogen Storage Diseases and Myoclonus

Protein tyrosine phosphatase non‑receptor 18 (PTPN18) is widely expressed in breast cancer (BC) cell lines. Additionally, high levels of PTPN18 facilitate an improved overall survival and prognosis in patients with BC. However, the effects and mechanisms of PTPN18 in BC remain unclear. In the present study, it was found that PTPN18 serves a tumor suppressor role in BC cells by promoting apoptosis, inhibiting proliferation and metastasis and inducing cell cycle arrest. Bioinformatics analysis showed that PTPN18 was significantly negatively correlated with the cell cycle and downregulated cyclin E expression, which was consistent with the experimental results. Subsequent co‑immunoprecipitation assay results showed that PTPN18 could bind to cyclin E and promote its degradation through the ubiquitin‑proteasome pathway. Moreover, the addition of cyclin E2 did not reduce the binding of PTPN18 to cyclin E1. In the present study, the signaling pathways involved in cell cycle regulation were further investigated and it was found that PTPN18 may regulate the expression levels of cyclin‑dependent kinase (CDK) inhibitor 1A and CDK inhibitor 1B proteins through phosphatidylinositol 3‑kinase/protein kinase B signaling pathway, which leads to cell cycle arrest and tumor inhibition in BC. Thus, analysis of the tumor suppressor mechanism of PTPN18 not only helps us to understand its biological function but also provides a theoretical basis for the development of new therapeutic strategies for...