PTP4A3 (Protein Tyrosine Phosphatase 4A3)

With this activation of P38/STAT1 pathway, the secretion of C-X-C motif chemokine ligand 12 (CXCL12) from F4/80+ macrophages is significantly improved, which could enhance the recruitment of MDSCs into the liver and impair the hepatic infiltration of CD8+ T cells, ultimately leading to the liver PMN formation and CLM. Taken together, our findings not only uncover the important role of PRL-3 in CLM via promoting the liver PMN formation, but also provide the evidence for the treatment of CLM by targeting PRL-3.

In the two external GEO (GSE71014 and GSE6891) datasets, area under the curve values of 1, 3, 5 years were 0.847, 0.857, 0.822, and 0.830, 0.863, 0.891 respectively. Our seven signature genes containing risk-scoring model performed excellently in evaluating the OS of AML patients.

This study provides an integrative single-cell and spatial atlas of CRC, revealing structured epithelial-T cell communication and spatial architecture within the tumor microenvironment. Our findings offer novel insights into immune-epithelial crosstalk and identify signaling pathways that may serve as therapeutic targets or biomarkers for CRC precision treatment.

Furthermore, it rescued the growth capacity of an inducible PRL-3-expressing three-dimensional intestinal cell culture organoid system derived from a PRL-3 overexpressing mouse line, mimicking the rescue of intestinal self-renewal capacity. The results introduce PRLthiophenib as a complementary inhibitor to published ones and support drug discovery efforts toward therapeutic targeting of this challenging cancer-promoting phosphatase.

Gene silencing of PTP4A3 resulted in the upregulation of compensatory mechanisms that overcame the loss of PTP4A3 expression, but this was mitigated by pan-PTP4A inhibition with JMS-053 in HGSOC cells. Moreover, shRNA-mediated silencing of PTP4A3 sensitised HGSOC cells to clinically relevant chemotherapeutic drugs. Overall, we show that compensatory mechanisms from PTP4A1 and PTP4A2 can arise when specifically targeting PTP4A3 in HGSOC and that pan-PTP4A inhibition can overcome those effects.

The IMEm7G gene signature established in our study effectively optimized the risk classification and predicted immunotherapy response in AML. Moreover, dactolisib was identified and demonstrated cytostatic activity alone and synergistic effects with doxorubicin in AML cells.

Interestingly, the absence of positive influence of gonadectomy on tumor behavior highlights the need for further research regarding this form of prevention. High expression of PRL receptor and VEGF only in distant metastases may prompt future research on the proangiogenic function of PRL in feline mammary gland tumors.

By demonstrating that PRL-3 enhances cancer progression independently of its catalytic activity, this study shifts focus toward targeting its binding functions as a therapeutic strategy. This study demonstrates that PRL-3 drives cancer initiation and progression through a phosphatase-independent mechanism across diverse models, highlighting the need to therapeutically target its non-catalytic protein interactions in future cancer treatment strategies.

The plasma PRL level and PRL-R expression in tumor tissue may be prognostic for Chinese postmenopausal women with breast cancer. The inhibition of PRL and PRL-R signaling is a potential therapeutic approach for endocrine therapy in breast cancer.

Targeted therapies against PRL-3, encompassing small molecule inhibitors and the monoclonal antibody PRL-3-zumab, have shown promise in clinical and preclinical studies, presenting new avenues for cancer treatment. In addition, innovative approaches such as CAAX motif-targeting agents and PRL-3 degradation strategies hold promise for developing more precise and effective interventions. This review explores PRL-3's multifaceted roles across different tumor types and microenvironments, while discussing current and emerging therapeutic strategies aimed at exploiting its oncogenic potential.