2. Academic Validation
  3. Cytoplasmic localization of IRF5 induces Wnt5a/E-cadherin degradation and promotes gastric cancer cells metastasis

Cytoplasmic localization of IRF5 induces Wnt5a/E-cadherin degradation and promotes gastric cancer cells metastasis

  • Cancer Gene Ther. 2023 Feb 13. doi: 10.1038/s41417-023-00596-0.
Jun Du # 1,  Chongqi Sun # 2,  Jiaojing Liu 3,  Xiaoli Wang 1,  Xuyang Zhao 1,  Yueyuan Wang 1,  Yadong Ma 1,  Hui Xie 4,  Chenxiang Qi 1,  Qianwen Wang 1,  Tianxiang Xia 1,  Fengwen Ye 1,  Yujie Zhang 5
Affiliations

Affiliations

  • 1 Department of Physiology, Nanjing Medical University, Nanjing, P.R. China.
  • 2 Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
  • 3 Assisted Reproductive Centre, Shandong Provincial Maternal and Child Health Care Hospital, Jinan, P.R. China.
  • 4 Department of Implantology, Changzhou Stomatological Hospital, Changzhou, P.R. China.
  • 5 Department of Physiology, Nanjing Medical University, Nanjing, P.R. China. [email protected].
  • # Contributed equally.
PMID: 36782048 DOI: 10.1038/s41417-023-00596-0
Abstract

IRF5, a nucleoplasm shuttling protein, is a pivotal transcription factor regulating immune system activity. It's well known that immunosuppression is involved in the development of gastric Cancer. However, no data exist for the expression and function of IRF5 in gastric Cancer. This study demonstrated that IRF5 was cytoplasm-enriched in gastric Cancer cells. IRF5 promoted gastric Cancer cell migration, which involved the inhibition of Wnt5a and E-cadherin proteins expression. IRF5 (LA) localized in nucleus had no significant effect on Wnt5a and E-cadherin expressions, while mutation of IRF5 (ΔNLS), which prevents IRF5 nuclear translocation, had more impact on these inhibitory effects. In addition, degradation rates of both Wnt5a and E-cadherin were enhanced by resiquimod, an IRF5 agonist. Further in vivo experiments indicated that IRF5 knockout of gastric Cancer cells repressed their pulmonary metastasis in nude mice. Finally, the expression and clinical significance of IRF5 were analyzed using gastric Cancer tissue microarrays, which suggested that the expression of IRF5 varied procedurally in different progressive stages of gastric Cancer. Our data revealed that IRF5 cytoplasmic localization were associated with Wnt5a and E-cadherin degradation and gastric Cancer cell metastasis. Inhibiting IRF5 expression and/or its cytoplasmic localization may provide a novel target for gastric Cancer therapy.

Figures
Products