2. Academic Validation
  3. MYSM1 promotes lung adenocarcinoma progression via TRAF2/3-mediated activation of MAPK and non-canonical NF-κB pathways

MYSM1 promotes lung adenocarcinoma progression via TRAF2/3-mediated activation of MAPK and non-canonical NF-κB pathways

  • NPJ Precis Oncol. 2025 Oct 29;9(1):337. doi: 10.1038/s41698-025-01116-z.
Wenhao Yu 1,  Luyuan Ma 1,  Rongyang Li 1,  Dingqiang Zhu 1,  Chenghao Qu 1,  Jingyi Han 1,  Yu Tian # 2,  Hui Tian # 3,  Jinghui Liang # 4
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
  • 2 Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. tianyu930314@126.com.
  • 3 Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. tianhuiql@email.sdu.edu.cn.
  • 4 Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. liangjhui@hotmail.com.
  • # Contributed equally.
PMID: 41162619 DOI: 10.1038/s41698-025-01116-z
Abstract

MYSM1, a deubiquitinating enzyme, is markedly overexpressed in lung adenocarcinoma (LUAD) and correlates with advanced disease stage and poor prognosis. Functional assays demonstrated that MYSM1 promotes LUAD cell proliferation and migration in vitro and in vivo. Mechanistically, MYSM1 interacts with TRAF2 and TRAF3 via its SWIRM domain, removing K63-linked polyubiquitin chains to decrease TRAF2-TRAF3 complex stability. This process impairs NIK degradation and sustains non-canonical NF-κB activation while simultaneously promoting MAPK (p38, JNK) signal pathway. Rescue experiments indicate that inhibiting TRAF2 or TRAF3 can attenuate MYSM1-induced activation of the MAPK pathway. These findings identify MYSM1 as a novel regulator of TRAF2-TRAF3 complex stability and a potential prognostic biomarker and therapeutic target in LUAD.

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