PTP4A2 Promotes Glioblastoma Progression and Macrophage Polarization Under Microenvironmental Pressure.

Phosphatase of Regenerating Liver-2 (PRL2; also known as PTP4A2) has been linked to cancer progression. Still, its exact role in glioblastoma (GB), the most aggressive type of primary brain tumor, remains elusive. Here we report that pharmacological treatment using JMS-053, a pan-PRL inhibitor, inhibits GB cell viability and spheroids growth. We also show that PTP4A2 is associated with a poor prognosis in gliomas, and its expression correlates with GBM aggressiveness. Using a GB orthotopic xenograft model, we show that PTP4A2 overexpression promotes tumor growth and reduces mouse survival. Furthermore, PTP4A2 deletion leads to increased apoptosis and pro-inflammatory signals. Using a syngeneic GB model, depletion of PTP4A2 reduces tumor growth and induces a shift in the tumor microenvironment towards an immunosuppressive state. In vitro assays show that cell proliferation is not affected in PTP4A2 deficient or overexpressing cells highlighting the importance of the microenvironment in PTP4A2 functions. Collectively, our results indicate that PTP4A2 promotes GB growth in response to microenvironmental pressure and supports the targeting of PTP4A2 as therapeutic strategy against GB.