ANO1 promotes malignant progression and epithelial–mesenchymal transition in head and neck squamous cell carcinoma through ERK/YAP-associated signaling

Background Anoctamin 1 (ANO1), a calcium-activated chloride channel encoded by TMEM16A, has been implicated in the progression of multiple human malignancies. However, its clinical significance, biological function and underlying molecular mechanisms in head and neck squamous cell carcinoma (HNSCC) remain incompletely understood. This study aimed to investigate the expression pattern, prognostic value and functional role of ANO1 in HNSCC. Methods ANO1 expression and its clinical significance were evaluated using The Cancer Genome Atlas (TCGA) database. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and immune infiltration analyses, were performed to explore the biological functions associated with ANO1. ANO1 expression was further validated in HNSCC tissues and cell lines by immunohistochemistry, quantitative real-time PCR and western blotting. Gain- and loss-of-function experiments were conducted to investigate the effects of ANO1 on cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT). The potential association between ANO1 and the ERK/YAP signaling pathway was subsequently evaluated. Results ANO1 was significantly overexpressed in HNSCC and was associated with poor prognosis and lymph node metastasis. Bioinformatics analyses indicated that ANO1 was involved in immune regulation, extracellular matrix remodeling and cell motility. Clinical specimens and HNSCC cell lines consistently exhibited elevated ANO1 expression. Functional experiments demonstrated that ANO1 depletion significantly inhibited cell proliferation, migration and invasion, whereas ANO1 overexpression enhanced clonogenic growth. Moreover, silencing ANO1 suppressed EMT by increasing E-cadherin expression and decreasing N-cadherin and Vimentin expression. Mechanistically, ANO1 depletion reduced ERK phosphorylation, decreased YAP expression and downregulated the YAP target genes CTGF and CYR61, suggesting that the tumor-promoting effects of ANO1 are associated with activation of the ERK/YAP signaling pathway. Conclusions Our findings demonstrate that ANO1 promotes the malignant progression of HNSCC and is associated with activation of the ERK/YAP signaling pathway. ANO1 may serve as a promising prognostic biomarker and potential therapeutic target for HNSCC.