ENPP2 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 2)

These findings decipher the cellular signatures and their interactions within the TME, shedding light on the inter-tumoral heterogeneity driven by different infections, and the development of targeted therapies for infectious HCC.

CCND2, NFASC, ENPP2, EPHA4 and SOX10 were identified to be candidate markers during melanoma progression. The proposed prognostic model had good predictive precision, which may be used for clinical prediction of melanoma development.

Spearman's correlation analysis identified ENPP2 as a key mediator of immune escape, with a strong positive correlation with PD-1 (r = 0.46, p = 8.7e-24). This 9-gene ferroptosis-related model provides a robust tool for OS prediction in Luminal A subtype breast cancer and highlights ENPP2 as a potential target for combining ferroptosis inducers with immune checkpoint inhibitors-offering a novel strategy for endocrine-resistant patients.

In this study, we constructed an MFRS model to predict patient prognosis and therapeutic response. This study also preliminarily reveals the roles of M2Ms and ferroptosis in HNSCC patients and provides potentially novel insight for treatment.

Taken together, our findings unravel the lipid metabolism characteristics of CLL. Moreover, we demonstrate a previously unidentified role and mechanism of ENPP2 in regulation of lipid metabolism, providing a novel therapeutic target for CLL treatment.

IF demonstrated that ENPP2 increased the expression of AR, suggesting a regulatory role for ENPP2 in hormonal response within PCOS and EC. Our findings indicated a significant correlation between ENPP2 expression and the modulation of immune responses.

Using the clinical-stage ATX inhibitor, IOA-289, we identified connective tissue growth factor (CTGF) as a downstream mediator of ATX signaling in the PDAC CAF-derived cell line, 0082T...Despite the loss of ATX function, extracellular levels of LPA were paradoxically increased, indicating a role for ATX beyond its enzymatic activity and suggesting a role for its LPA chaperone function in the LPA/LPAR signaling in CAFs. As CAFs are the main source for CTGF in the PDAC TME, these findings suggest a role for ATX in promoting pro-tumorigenic microenvironment via modulation of CAF secretion, not only via its LPA-producing activity but also via its LPA chaperone function, providing a potential mechanism for the anti-tumor effects of ATX inhibition.

Our study used two prognosis-favorable genes to divide M2-like TAMs of PDAC into anti-tumor bM2-like TAMs and pro-tumor mM2-like TAMs. The bM2-like TAMs activate T cells through ALCAM/CD6 and generate prognosis-favorable αSMA+ myofibroblasts through secreting TGFβ, which brings insight into heterogeneity of TAMs, prognosis prediction and immunotherapy of PDAC.

Based on these observations, clinical trials with ATX-targeted drugs and standard chemotherapy regimens may benefit from selecting GEA patients based on their levels of ATX, LPA and CEA.

In vivo pharmacokinetic and antitumor studies showed promising results, with 7 not only exhibiting efficient pharmacokinetic properties but also enhancing the antitumor efficacy of the anti-PD-1 antibody. Treatment with 7 (80 mg/kg) combined with anti-PD-1 antibody achieved a tumor growth inhibition rate of 77.7% and improved survival in a murine model.

Additionally, we observed that the reduction of ENPP2 alleviates melanoma cell migration and invasion, due to the changes of cholesterol metabolism and ECM remodeling. Based on these findings, we demonstrated that M1 macrophages suppress aggressiveness of melanoma cells via exosomal miR-29c-3p-mediated knock-down of ENPP2 in cancer cells.

LPAR2 and PLPP2 inhibition are also predicted to have potential therapeutic utility. Future multi-omics investigations are necessarily to validate which LPA signaling components are high-value candidates for pharmacological manipulation in PDAC treatment.