Dual Role of the PTPN13 Tyrosine Phosphatase in Cancer.

In this review article, we present the current knowledge on PTPN13, a class I non-receptor protein tyrosine phosphatase identified in 1994. We focus particularly on its role in cancer, where PTPN13 acts as an oncogenic protein and also a tumor suppressor. To try to understand these apparent contradictory functions, we discuss PTPN13 implication in the FAS and oncogenic tyrosine kinase signaling pathways and in the associated biological activities, as well as its post-transcriptional and epigenetic regulation. Then, we describe PTPN13 clinical significance as a prognostic marker in different cancer types and its impact on anti-cancer treatment sensitivity. Finally, we present future research axes following recent findings on its role in cell junction regulation that implicate PTPN13 in cell death and cell migration, two major hallmarks of tumor formation and progression.

The Effect of Denatured Flagellin on Toll-Like Receptor-5 (TLR-5) in Mice.

BACKGROUND: Previous studies have demonstrated that flagellin, a component of bacterial flagella, engages Toll-Like receptor 5 (TLR-5) causing the activation of the Myeloid Differentiation Factor-88 (MYD-88) pathway that leads to the production of pro-inflammatory cytokines including Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). In physiological levels, cytokines can aid in protection against infectious agents. However, excessive production of cytokines can lead to septic shock during sepsis. OBJECTIVE: In this study, we aimed at investigating the effect of denatured flagellin on hindering the effects induced by intact flagellin or flagellated Pseudomonas aeruginosa on the Toll-Like Receptor-5 (TLR-5) in mice. METHODS: Mouse mononuclear cells (MNCs) were cultured with intact flagellin, heat-denatured flagellin, TLR-5 antagonist, Pseudomonas aeruginosa, and TLR-4 antagonist each alone or in combinations. Supernatants were collected at 4 hours post incubation to assess the levels of IL-12 and TNF-α by Enzyme-Linked ImmunoAssay (ELISA). Furthermore, groups of BALB/c mice were injected intraperitoneally (IP) with Pseudomonas aeruginosa, LPS-RS, intact flagellin, and denatured flagellin, each alone or in different combinations. Serum levels of IL-12 and TNF-α were measured at 2, 4, and 6 hours post injections of Pseudomonas aeruginosa or intact flagellin. RESULTS: Pretreatment with denatured flagellin significantly reduced the amount of TNF-α and IL-12 produced both in vitro and in vivo by intact flagellin or Pseudomonas aeruginosa. CONCLUSION: Denatured flagellin suppressed the production of the pro-inflammatory cytokines induced by intact flagellin or Pseudomonas aeruginosa both in vitro and in vivo, probably by blocking TLR5. Denatured flagellin might be considered as an anti-septic shock agent.