Work

Protocadherin gamma subfamily A, 3 inhibits the proliferation and metastasis of lung adenocarcinoma by inhibiting transforming growth factor β signaling pathway

Year: 2026

Type: article

Abstract: BACKGROUND: Lung adenocarcinoma (LUAD) is a prevalent malignancy with poor clinical prognosis, and the specific role of PCDHGA3 in LUAD pathogenesis remains to be fully clarified and understood. METHODS: TCGA, UCSC XENA, and Human Protein Atlas databases were comprehensively utilized to systematically analyze PCDHGA3 expression levels, clinical prognostic significance, DNA methylation status, and mutation patterns. GO, KEGG, and GSEA enrichment analyses were performed to identify related biological pathways and functions. Western blotting, wound healing assays, cell adhesion assays, CCK8 proliferation assays, and transwell migration assays evaluated PCDHGA3 biological functions. Animal models were employed to validate in vivo effects and mechanisms. RESULTS: PCDHGA3 demonstrated low expression in LUAD tissues. High mutation rates and altered methylation patterns indicated potential involvement in LUAD development. PCDHGA3 overexpression notably inhibited cancer cell proliferation and migration abilities in both in vitro and in vivo models. Moreover, PCDHGA3 overexpression markedly elevated E-cadherin protein levels while substantially reducing N-cadherin, phospho-SMAD2, phospho-SMAD3, and TGFβ protein levels. CONCLUSION: PCDHGA3 inhibits LUAD progression and metastasis by suppressing the TGFβ signaling pathway, providing novel therapeutic insights.

Source: Respiratory Research

DOI: 10.1186/s12931-026-03633-2