NR4A1 (Nuclear Receptor Subfamily 4 Group A Member 1)

In a phase 1b trial (ARC-8), we evaluated safety and efficacy of quemliclustat combined with gemcitabine/nab-paclitaxel (G/nP) with or without zimberelimab (anti-programmed cell death protein 1 (PD-1)) in first-line metastatic pancreatic ductal adenocarcinoma (PDAC)...High tumor NR4A expression was associated with improved overall survival (OS) in ARC-8 but not in two external cohorts from the PRINCE (G/nP + nivolumab (nivo)) or Morpheus-PDAC (G/nP) trials...In paired pretreatment/posttreatment biopsies, maximal downregulation of NR4A expression was associated with T cell activation and improved OS, pointing to a biological link between tumor adenosine and clinical benefit. ClinicalTrials.gov identifier: NCT04104672 .

Brewed coffee and several polyphenolics, including caffeic acid, ferulic acid, chlorogenic acid, p-coumaric acid, several cinnamic acid derivatives, kahweol, and cafestrol, bound NR4A1 in binding assays, and most Kd values were <10 µM... The results of this study demonstrate that brewed coffee and its major polyphenolics and polyhydroxy constituents are NR4A1 ligands and that NR4A1 may play an important role in the health-protective effects of coffee. These results, coupled with recent studies, indicate that NR4A1 and its ligands may play an important role in diet and health.

This transcriptomic analysis confirms ECM dysregulation as a core feature of IPF pathogenesis and highlights novel DEGs and hub genes with potential roles in fibrosis, providing a foundation for future functional and translational studies.

AE infection drives a transition from acute inflammation to chronic immune regulation through extensive lineage diversification and functional reprogramming of CD8+ T cells. Spatially organized DC-T-cell interactions likely contribute to maintaining a regulated yet immunologically active microenvironment, providing insights for targeting chronic-stage immune responses in AE.

These findings establish the NR4A1 promoter as a native, activation-inducible system to fine-tune CAR expression, while maintaining therapeutic efficacy comparable to constitutively expressed CAR T cells. This strategy provides a promising framework for advancing CAR T cell therapies against solid tumors.

These findings indicate that NR4A1 is involved in the anxiety-like behavior induced by alcohol withdrawal through reversing the anti-apoptotic function of BCL2 and promoting the expression of BAX and caspase3.

This is one of the most comprehensive single-cell studies of leukaemic CTCL to date. We uncover new malignant T-cell states, broaden the known repertoire of KIR expression, and propose mechanisms of immune evasion that may contribute to treatment resistance. These findings lay the groundwork for subtype-specific and microenvironment-informed therapeutic strategies in Sézary syndrome, with potential implications for guiding targeted therapy selection but require validation in larger, independent cohorts.

Collectively, these findings identify ALDH2 as a key tumor suppressor in HNSC, including OSCC, and highlight the therapeutic potential of activating ALDH2, NR4A1, and TGM2. Moreover, stabilization of the ALDH2-ALDH6A1 complex may offer a viable strategy for disease prevention and treatment, even in the context of frequent ALDH2 mutations.

To investigate oxaliplatin (OXA)‑induced senescence in GC cells, cellular senescence was assessed by senescence‑associated β‑galactosidase (SA‑β‑Gal) staining, western blotting, immunofluorescence, and reverse transcription‑quantitative polymerase chain reaction for the senescence‑associated secretory phenotype (SASP) factors...The present study identified NR4A1 as a key regulated gene in chemotherapy‑induced senescence in GC and verified that the NR4A1/AKT‑metabolism axis is vital for the pivotal mechanism of TIS. These findings may provide a novel therapeutic strategy to optimize chemotherapy and develop 'one‑two punch' approaches targeting senescent tumor cells.

These findings suggest that DEP may promote endometrial carcinogenesis by triggering oxidative stress-mediated signaling crosstalk and accelerating cell cycle progression. This study establishes a multi-layered methodological framework-from computational screening and machine learning to experimental validation-offering novel mechanistic insights into the carcinogenic potential of environmental endocrine disruptors such as DEP.

This study provides new insights into the molecular mechanisms underlying the progression of GBM, emphasizing the role of SERPINE1 and its interaction with NR4A1 in promoting EMT and tumor invasion. Inhibiting the expression of SERPINE1 in GBM cells can prevent cell invasion, providing a potential strategy for the treatment of GBM.

Mechanistically, IL-6 drives formation of an immunosuppressive TIME by promoting protumour macrophage polarisation. This, in turn, suppress cytotoxic T cell infiltration, promoting Treg expansion, and impairing NK cell function, indicating that the targeting of IL-6 represents a promising strategy to overcome resistance to chemoimmunotherapy.