2. Academic Validation
  3. SERPINH1 promotes malignant progression of laryngeal squamous cell carcinoma via COL7A1-mediated Wnt/β-catenin signaling

SERPINH1 promotes malignant progression of laryngeal squamous cell carcinoma via COL7A1-mediated Wnt/β-catenin signaling

  • Cell Signal. 2025 Nov:135:112043. doi: 10.1016/j.cellsig.2025.112043.
Feinan He 1,  Jinqiu Li 1,  Weifang Tong 1,  Sanchun Wang 1,  Hongyan Wang 1,  Baishuo Huang 1,  Bo Teng 2
Affiliations

Affiliations

  • 1 The Second Hospital of Jilin University, Department of Otorhinolaryngology, China.
  • 2 The Second Hospital of Jilin University, Department of Otorhinolaryngology, China. Electronic address: tengbo@jlu.edu.cn.
PMID: 40752536 DOI: 10.1016/j.cellsig.2025.112043
Abstract

Background: Serpin peptidase inhibitor clade H member 1 (SERPINH1) is implicated in Collagen processing and tumor progression, yet its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. This study aimed to elucidate the clinical significance and molecular mechanism of SERPINH1 in LSCC.

Methods: Multi-cohort bioinformatics analysis (TCGA, GEO) identified SERPINH1 as a prognostic marker. SERPINH1 expression was validated in LSCC tissues (IHC, immunofluorescence, Western blot). Functional assays (CCK-8, EdU, Transwell) and xenograft models assessed malignant behaviors. Transcriptomics and co-IP/LC-MS revealed downstream pathways and interactors. Wnt agonist (SKL2001) rescue experiments confirmed pathway dependency.

Results: SERPINH1 was overexpressed in LSCC tissues versus adjacent normal and predicted poor survival. SERPINH1 knockdown suppressed proliferation, migration/invasion, and tumor growth in vitro and in vivo. Mechanistically, SERPINH1 bound COL7A1 to stabilize the Wnt/β-catenin signaling complex, reducing β-catenin phosphorylation and enhancing nuclear translocation. Wnt activation via SKL2001 rescued SERPINH1-knockdown phenotypes.

Conclusion: SERPINH1 drives LSCC progression via COL7A1-mediated Wnt/β-catenin signaling activation. Targeting this axis may offer novel therapeutic strategies for LSCC.

Keywords

COL7A1; Epithelial-mesenchymal transition; Laryngeal squamous cell carcinoma; SERPINH1; WNT/β-catenin signaling.

Figures
Products