Academic Journal
ENOX1 promotes gastric cancer progression via Snail2-mediated epithelial-mesenchymal transition and M2-type tumour-associated macrophages polarisation.
| Τίτλος: | ENOX1 promotes gastric cancer progression via Snail2-mediated epithelial-mesenchymal transition and M2-type tumour-associated macrophages polarisation. |
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| Συγγραφείς: | Fu Q; Qinghai University Affiliated Hospital (The Clinical Medical School), Qinghai University, Xining 810000, China., Di J; Qinghai University Affiliated Hospital (The Clinical Medical School), Qinghai University, Xining 810000, China.. Electronic address: luosangdj@126.com. |
| Πηγή: | International immunopharmacology [Int Immunopharmacol] 2026 Oct 01; Vol. 186, pp. 117090. Date of Electronic Publication: 2026 Jul 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| Ιατρικοί όροι (MeSH): | Snail Family Transcription Factors*/metabolism , Snail Family Transcription Factors*/genetics , Stomach Neoplasms*/pathology , Stomach Neoplasms*/immunology , Stomach Neoplasms*/genetics , Stomach Neoplasms*/metabolism , Tumor-Associated Macrophages*/immunology , Tumor-Associated Macrophages*/metabolism , Epithelial-Mesenchymal Transition*, Humans ; Animals ; Cell Line, Tumor ; Mice ; Tumor Microenvironment ; Disease Progression ; Female ; Male ; Gene Expression Regulation, Neoplastic ; Cell Movement |
| Περίληψη: | Remodelling of the tumour microenvironment drives gastric cancer progression; however, the mechanism by which ecto-nicotinamide adenine dinucleotide oxidase 1 (ENOX1) regulates this process remains unknown. In the present study, we investigated the oncogenic functions of ENOX1 in gastric cancer. Analysis of public datasets and clinical samples revealed that ENOX1 was significantly overexpressed in gastric cancer tissues and correlated with poor prognosis. In vitro functional assays demonstrated that ENOX1 knockout suppressed the proliferation, migration, invasion, and clonogenicity of gastric cancer cells. Mechanistically, RNA sequencing and subsequent verification revealed that ENOX1 upregulates Snail2 expression and promotes epithelial-mesenchymal transition (EMT). Furthermore, ENOX1 expression in gastric cancer cells promotes the polarisation of co-cultured macrophages towards immunosuppressive M2-type tumour-associated macrophages (TAMs), as evidenced by the increased expression of CD206 and CD163. Rescue experiments indicated that Snail2 overexpression reverses the inhibitory effects of ENOX1 knockout on EMT and M2-type TAM polarisation. In an orthotopic mouse model, ENOX1 knockdown potently suppressed AKT/MYC-driven gastric tumourigenesis, reversed the EMT phenotype, and reduced M2-type TAM infiltration into tumour tissues. Collectively, our findings reveal that ENOX1 may promote gastric cancer progression via Snail2-mediated EMT and M2-type TAM polarisation, suggesting that ENOX1 is a potential therapeutic target. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: ENOX1; Epithelial-mesenchymal transition; Gastric cancer; M2-type tumour-associated macrophages; Tumour microenvironment |
| Substance Nomenclature: | 0 (Snail Family Transcription Factors) 0 (SNAI1 protein, human) |
| Entry Date(s): | Date Created: 20260704 Date Completed: 20260809 Latest Revision: 20260809 |
| Update Code: | 20260810 |
| DOI: | 10.1016/j.intimp.2026.117090 |
| PMID: | 42401092 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2026.117090 |