Panoply™ Human PTPN2 Knockdown Stable Cell Line

PTPN2 belongs to the non-receptor protein tyrosine phosphatase family and plays a crucial role in tumorigenesis and cancer immunotherapy. Here, our research shows that PTPN2 is highly expressed in most cancers and is associated with poor prognosis in adenoid cystic carcinoma (ACC), glioblastoma (GBM), low-grade glioma (LGG), renal cell carcinoma (KICH), and pancreatic adenocarcinoma (PAAD), but the opposite is true in ovarian cancer (OV), skin cancer (SKCM), and thymic carcinoma (THYM). PTPN2 knockdown promotes the proliferation of melanoma cells while significantly inhibiting the proliferation of colon cancer and glioblastoma cells. Furthermore, the TC-PTP encoded by the PTPN2 gene is mainly located in the nucleus and cytoplasm and negatively regulates the JAK/STAT and MEK/ERK signaling pathways. Notably, PTPN2 knockdown significantly enhances PD-L1 expression. PTPN2 is highly expressed in monocytes/macrophages and is positively correlated with various immune infiltrating cells, especially CD8+ T cells. These studies suggest that the immune checkpoint PTPN2 is a potent biomarker for predicting cancer prognosis and the efficacy of immunotherapy. Mechanistically, PTPN2 negatively regulates the expression of the JAK/STAT and MEK/ERK pathways, as well as PD-L1.

Immunofluorescence images showed that TC-PTP was primarily located in the nucleus, followed by the cytoplasm, in A375, HCT116, SKOV3, and U87 cell lines (Figure 1A). PTPN2-related genes are mainly involved in multiple oncogenic pathways, such as the JAK/STAT, EGFR, and programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling pathways, and are closely related to the development and progression of human cancers (Figure 1B and 1C). Here, researchers constructed PTPN2 knockdown A375, HCT116, and U87 cells. To more fully mimic the in vivo tumor cell microenvironment in vitro, researchers induced and stimulated cells using IFN-γ. The results showed that PTPN2 knockdown promoted STAT1 phosphorylation in A375 and HCT116 cells and significantly activated the JAK1/STAT1 pathway, while no significant changes were observed in U87 cells. Notably, PD-L1 expression was stimulated to varying degrees in all three PTPN2 knockdown cell lines, with the most significant effect observed in A375 cells (Figure 1D). Next, to investigate the effects of PTPN2 on downstream targets of the EGFR pathway, we first treated cells with epidermal growth factor (EGF). The results showed that in PTPN2 knockdown A375 and HCT116 cells, STAT3 phosphorylation and JAK/STAT3 pathway activation were promoted, while in PTPN2 knockdown U87 cells, extracellular signal-regulated kinase (ERK) phosphorylation and MEK/ERK pathway activation were enhanced (Figure 1E). Overall, PTPN2 can dephosphorylate the substrate proteins STAT1/3 and ERK and negatively regulate PD-L1 expression.

Figure 1. Cellular localization and molecular function of PTPN2. (Tang X, et al., 2023)