SERPINH1 promotes malignant progression of laryngeal squamous cell carcinoma via COL7A1-mediated Wnt/β-catenin signaling
Published:31 July 2025
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.