Abbreviations: AAV: adeno-associated virus; ACTB/β-actin: actin, beta; AIF1/IBA1: allograft inflammatory factor 1; BAF: bafilomycin A1; BNIP3: BCL2/adenovirus E1B interacting protein 3; CCI: controlled cortical impact; COX8: cytochrome c oxidase subunit 8; CUT&Tag: cleavage under targets and tagmentation; DAPI: 4,'6-diamidino-2-phenylindole; DEGs: differentially expressed genes; eGFP: enhanced green fluorescent protein; EGR1: early growth response 1; GFAP: glial fibrillary acidic protein; GO: gene ontology; GSEA: gene set enrichment analysis; HCQ: hydroxychloroquine; HIF1A/HIF-1α: hypoxia inducible factor 1, alpha subunit; IGV: integrative genomics viewer; KEGG: Kyoto encyclopedia of genes and genomes; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; Lv: lentivirus; MAP2: microtubule-associated protein 2; mCherry: monomeric cherry fluorescent protein; mRFP: monomeric red fluorescent protein; MTOR: mechanistic target of rapamycin kinase; MUT: mutant; MWM: Morris water maze; NAB1: Ngfi-A binding protein 1; NAB2: Ngfi-A binding protein 2; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; OGD: oxygen-glucose deprivation; OLIG2: oligodendrocyte transcription factor 2; PBS: phosphate-buffered saline; PECAM1/CD31: platelet/endothelial cell adhesion molecule 1; PFA: paraformaldehyde; PPI: protein-protein interaction; Puro: puromycin; ROI: region of interest; ROS: reactive oxygen species; SEM: standard error of the mean; SQSTM1/p62: sequestosome 1; TBI: traumatic brain injury; TOMM20: translocase of outer mitochondrial membrane 20; TSA: tyramide signal amplification; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; VDAC1: voltage-dependent anion channel 1; WT: wild-type.

As the galectin-3/EGR1 complex acted as a key node relaying pro-invasive signaling, its disruption using GB1107, an oral galectin-3 inhibitor, suppressed tissue infiltration and metastasis of patient-derived xenografts. Taken together, a pro-invasive galectin-3/EGR1 transcriptional complex was exploited by TRIM49-deficient GAC to fuel tissue invasion, representing an Achilles'heel that is potentially targetable to prevent metastasis.

The combined effects of elevated EGR1 expression, along with signaling pathways activated by KRAS and mutant p53, significantly enhance pro-metastatic traits in cancer cells. These findings provide crucial insights into the co-enrichment of KRAS and p53 mutations and pave the way for novel therapeutic strategies targeting this interaction.

This study highlights the miR-192/215-EGR1 axis as a critical regulator of GC progression and a promising therapeutic target. EGCG may serve as an adjunct therapy for GC. Future studies should focus on the regulatory mechanisms of EGR1, its interaction with the tumor microenvironment, and clinical validation of EGCG and other agents targeting this axis.

Our findings propose a novel therapeutic approach with rhRelaxin-2 for patients with atherosclerosis.

From the above experiments, we found that CtBP2 can regulate the Wnt/β-catenin signaling pathway through EGR1 to influence the proliferation and apoptosis of DLBCL cells. Therefore, EGR1 may be one of the key contributors involved in the regulation of Wnt/β-catenin signaling by CtBP2.

Furthermore, EGR1 can prevent the development and movement of ccRCC cells by controlling the expression of MMP-2, MMP-9, E-cadherin, and MAPK15. The EGR1/MAPK15 axis may represent a promising target for drug development, with EGR1 serving as a possible target for ccRCC therapy.

The adrenal cortex of pigs with secondary hyperaldosteronism shows decreased immunostaining of EGR1 and a marker of oxidative stress, suggesting a potential link between EGR1 expression, oxidative stress levels, and adrenocortical function. These findings reveal a novel mechanism linking EGR1 to oxidative stress regulation and aldosterone production in adrenal cells, with potential implications for the pathogenesis of APAs and other adrenocortical tumors.

Collectively, we revealed for the first time that PDE4 inhibitor Zl-n-91 could inhibit the growth of GBM cells through the EGR1/PTEN/AKT signaling pathway. Zl-n-91, a specific PDE4 inhibitor, may be a promising therapeutic candidate for GBM.

This study demonstrates that ketamine alleviates BC cell-induced osteoclastogenesis and tumor bone metastasis by suppressing SRC and restoring the EGR1/CST6 axis.

In conclusion, our findings demonstrated that durvalumab and T-DXd synergistically promoted apoptosis in cholangiocarcinoma cells by inhibiting EGR1 expression through inactivation of the p38 MAPK pathway. This study confirmed the potential of durvalumab and T-DXd for the treatment of cholangiocarcinoma.

These findings strongly support EGR-1's tumor-suppressive role in OSCC and hint at the potential for novel OSCC therapies aimed at restoring aberrant EGR-1 function.