TWF1 promotes tumor progression in head and neck squamous cell carcinoma via AKT phosphorylation

Objective: To investigate the molecular mechanisms underlying how Twinfilin actin-binding protein 1 (TWF1) drives the malignant progression of head and neck squamous cell carcinoma (HNSCC).

Design: A pan-cancer analysis of TCGA datasets was performed to evaluate TWF1 expression and prognostic significance, followed by validation using quantitative Real-Time PCR (qPCR) and immunohistochemistry (IHC) in clinical HNSCC specimens. Functional assays (CCK-8, colony formation, wound healing, and Transwell invasion) were conducted following siRNA-mediated TWF1 knockdown in SCC9 cells. Additionally, the same functional assays were conducted in an HSC3 cell model overexpressing TWF1 to further evaluate its oncogenic function. The involvement of the Akt signaling pathway was examined by Western blot and validated through rescue experiments with the Akt Activator SC79.

Results: TWF1 was found to be upregulated in 13 Cancer types, including HNSCC. Elevated TWF1 expression, advanced T stage, and lymph node metastasis were identified as independent prognostic indicators in HNSCC. qPCR confirmed increased TWF1 expression, and IHC showed higher TWF1 protein levels in HNSCC tissues. TWF1 knockdown suppressed SCC9 cell proliferation, migration, and invasion, and reduced phosphorylated Akt levels. Conversely, TWF1 overexpression in HSC3 cells promoted proliferation, migration, and invasion while enhancing Akt phosphorylation. SC79 treatment partially reversed the malignant phenotypes suppressed by TWF1 knockdown, supporting TWF1's regulatory role through Akt phosphorylation.

Conclusion: TWF1 acts as an oncogenic driver in HNSCC, promoting tumor progression through the Akt signaling pathway. It may serve as a potential therapeutic target in precision medicine for HNSCC.

AKT signaling pathway; HNSCC; TWF1.