2. Academic Validation
  3. Suppression of SENP3 enhances macrophage alternative activation by mediating IRF4 de-SUMOylation in ESCC progression

Suppression of SENP3 enhances macrophage alternative activation by mediating IRF4 de-SUMOylation in ESCC progression

  • Cell Commun Signal. 2024 Aug 9;22(1):395. doi: 10.1186/s12964-024-01770-z.
Shaoyuan Zhang # 1 2,  Jianmin Gu # 1 2,  Wenhan Wang # 3,  Linyi Sun 1 2,  Tian Jiang 1 2,  Xinyu Yang 1 2,  Jun Yin 1 2,  Miao Lin 1 2,  Dong Lin # 4,  Hao Wang # 5 6,  Lijie Tan # 7 8
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Xuhui District, No. 180, Fenglin Road, Shanghai, 200032, People's Republic of China.
  • 2 Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
  • 3 Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
  • 4 Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Hongkou District, No. 100, Haining Road, Shanghai, 200080, People's Republic of China. lin_dong@sjtu.edu.cn.
  • 5 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Xuhui District, No. 180, Fenglin Road, Shanghai, 200032, People's Republic of China. wang.hao@zs-hospital.sh.cn.
  • 6 Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. wang.hao@zs-hospital.sh.cn.
  • 7 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Xuhui District, No. 180, Fenglin Road, Shanghai, 200032, People's Republic of China. tan.lijie@zs-hospital.sh.cn.
  • 8 Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China. tan.lijie@zs-hospital.sh.cn.
  • # Contributed equally.
PMID: 39123188 DOI: 10.1186/s12964-024-01770-z
Abstract

Esophageal Cancer is common worldwide, with ESCC being the most frequent tumor in East Asia. Tumor-associated macrophages are an important component of the ESCC microenvironment. SUMOylation is a post-translational modification of proteins, and SUMO-specific proteases (SENPs) play an important role in de-SUMOylation. In human patients, we discovered that the levels of SENP3 were upregulated in the tumor-associated macrophages. Furthermore, the loss of SENP3 enhanced the alternative activation of macrophages in the 4-NQO-induced ESCC mice model. This is the first study to identify SENP3-mediated macrophage polarization via the de-SUMOylation of interferon regulatory factor 4 (IRF4) at the K349 site. Alternative activation of macrophages increases the migration and invasion potential of ESCC cells and promotes their progression in vivo. Moreover, patients with relatively low SENP3 expression in macrophages exhibit higher primary PET SUVmax value and lymph node metastasis rates. In summary, this study revealed that SENP3-mediated IRF4 de-SUMOylation is crucial for the alternative activation of macrophages and influences the progression of ESCC.

Keywords

Alternative activation; De-SUMOylation; Esophageal squamous cell carcinoma (ESCC); IRF4; SENP3; SUMOylation; Tumor-associated macrophage.

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