PTPN2 acts as a tumor suppressor and therapeutic target in ovarian cancer

Xiaoli Sun & Dao-Lai Zhang et al. · 2025-09-23

Ovarian cancer (OC) remains the most lethal gynecological malignancy, with metastasis and chemoresistance driving poor outcomes. Non-receptor protein tyrosine phosphatase 2 (PTPN2) is a critical regulator of oncogenic signaling pathways, but its role in OC progression remains poorly understood. Here, we identify PTPN2 as a critical tumor suppressor in OC through integrated bioinformatics and functional studies. Bioinformatics analysis revealed significant PTPN2 downregulation in OC tissues, correlating with advanced tumor stage and poor patient survival. Experimental validation confirmed reduced PTPN2 expression at both mRNA and protein levels in clinical specimens. Functional studies demonstrated that PTPN2 overexpression inhibits OC cell proliferation, migration, and motility. Mechanistically, PTPN2 maintains epithelial cell characteristics by upregulating E-cadherin while suppressing mesenchymal markers Snail and Twist through negative regulation of ERK1/2 phosphorylation. Our findings not only expand the current understanding of PTPN2's role in cancer biology but also suggest its dual potential as both a prognostic biomarker and a promising therapeutic target for OC treatment.
Authors
Xiaoli Sun, Wenkai Zhang, Hongmei Wang, Junmei Hao, Wenning Shi, Ping Lei, Guangyu Wei, Yusheng Liu, Cong Xu, Lianqin Li, Liting Yu, Dao-Lai Zhang
Funding

National Natural Science Foundation of China

81901548

National Natural Science Foundation of China

82371629

Natural Science Foundation of Shandong Province

ZR2023QC065

Natural Science Foundation of Shandong Province

ZR2024MC198

Natural Science Foundation of Shandong Province

2242021R41070