PTPN18 Stimulates the Development of Ovarian Cancer by Activating the PI3K/AKT Signaling.

Nan Mao,Hui Yang,Zhimin Liang,Hu Li,Guansheng He,Jianfen Su,Alamgeer Yuchi

doi:10.1155/2022/1091042

Abstract

Objective To illustrate the functions of protein tyrosine phosphatase nonreceptor type 18 (PTPN18) in the progression of ovarian cancer and the potential molecular mechanism. Methods Differential PTPN18 expression in ovarian cancer samples was determined. Following PTPN18 knockdown, changes in proliferation and migration in ovarian cancer cells were detected. Nude mice with ovarian cancer were used to uncover the effects of PTPN18 on ovarian cancer growth in vivo. Results PTPN18 was significantly upregulated in ovarian cancer samples and linked to pathological staging and metastasis rate. PTPN18 displayed prognostic and diagnostic potentials in ovarian cancer. Knockdown of PTPN18 and treatment of the PI3K inhibitor could inhibit proliferative and migratory abilities in ovarian cancer cells. Moreover, PTPN18 was capable of inactivating PI3K/AKT signaling. In vivo knockdown of PTPN18 suppressed ovarian cancer growth in nude mice. Conclusions PTPN18 is upregulated in ovarian cancer, which stimulates the malignant development by activating PI3K/AKT signaling. The PTPN18 level is also associated with pathological staging and metastasis in ovarian cancer patients, which may be utilized as a hallmark predicting the malignant level.

Highlights

Ovarian cancer (OC) is one of the most common gynecological malignancies [1, 2]
Despite improvements achieved in surgical techniques and chemotherapy, the effective treatment rate of advanced OC is only 15–20% [4–6]. e Wnt, Notch, Hedgehog, and PI3K signaling are believed to influence the development of ovarian cancer [7–10]
We found higher level of Protein tyrosine phosphatase nonreceptor type 18 (PTPN18) in OC tissues than paracancerous tissues (Figure 1(a))

Summary

Introduction

Ovarian cancer (OC) is one of the most common gynecological malignancies [1, 2]. Most patients are diagnosed as the advanced ovarian cancer or ovarian cancer accompanied by intraperitoneal implantation and metastasis, leading to a high mortality rate [1, 3]. Despite improvements achieved in surgical techniques and chemotherapy, the effective treatment rate of advanced OC is only 15–20% [4–6]. E Wnt, Notch, Hedgehog, and PI3K signaling are believed to influence the development of ovarian cancer [7–10]. Clarifying ovarian cancer-associated signaling contributes to block the recurrence and metastasis, improving the clinical outcomes [11, 12]. Protein tyrosine phosphatase nonreceptor type 18 (PTPN18) is the first discovered specific tyrosine phosphatase of human epidermal growth factor receptor 2 (HER2), which is closely linked to tumor development [13, 14]. Protein tyrosine phosphatases influence cell growth and other cellular functions under external stimuli [13]. PTPN18 has a strict substrate specificity, and it can only dephosphorylate the phosphorylated tyrosine residues of HER2 [13, 15]. PTPN18 negatively regulates HER2 tyrosine kinase activity mainly through selectively dephosphorylating the tyrosine phosphorylation site of HER2, thereby effectively regulating cell function [13]. It is able to inhibit the progression of chronic myeloid leukemia and to influence functions of hematopoietic stem cells [13, 14, 16]

Methods

Results

Conclusion