AI Article Synopsis

  • Phosphatase of regenerating liver 2 (PTP4A2) is linked to cancer progression, particularly in glioblastoma (GBM), where its role as a contributor to tumor aggressiveness is being investigated.
  • In experiments, inhibiting PTP4A2 with JMS-053 decreased GBM cell viability and tumor growth, while its overexpression in mouse models led to faster tumor development and reduced survival rates.
  • Depleting PTP4A2 not only heightened apoptosis and inflammation but also altered the tumor microenvironment, suggesting that targeting PTP4A2 could be an effective therapy for GBM by leveraging its dependency on the microenvironment for tumor growth.

Article Abstract

Unlabelled: Phosphatase of regenerating liver 2 (also known as PTP4A2) has been linked to cancer progression. Still, its exact role in glioblastoma (GBM), the most aggressive type of primary brain tumor, remains elusive. In this study, we report that pharmacologic treatment using JMS-053, a pan-phosphatase of regenerating liver inhibitor, inhibits GBM cell viability and spheroid growth. We also show that PTP4A2 is associated with a poor prognosis in gliomas, and its expression correlates with GBM aggressiveness. Using a GBM orthotopic xenograft model, we show that PTP4A2 overexpression promotes tumor growth and reduces mouse survival. Furthermore, PTP4A2 deletion leads to increased apoptosis and proinflammatory signals. Using a syngeneic GBM model, we show that depletion of PTP4A2 reduces tumor growth and induces a shift in the tumor microenvironment (TME) toward 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 GBM growth in response to microenvironmental pressure and support the rationale for targeting PTP4A2 as a therapeutic strategy against GBM.

Significance: High levels of PTP4A2 are associated with poor outcomes in patients with glioma and in mouse models. PTP4A2 depletion increases apoptosis and proinflammatory signals in GBM xenograft models, significantly impacts tumor growth, and rewires the TME in an immunocompetent host. PTP4A2 effects in GBM are dependent on the presence of the TME.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238266PMC
http://dx.doi.org/10.1158/2767-9764.CRC-23-0334DOI Listing

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