Abstract
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most prevalent cancer globally, with lymph node metastasis being a primary contributor to poor patient prognosis. Elucidating the molecular mechanisms driving HNSCC lymphatic metastasis is imperative for developing targeted therapeutic strategies and improving patient survival. METHODS: The expression of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in HNSCC samples was evaluated using The Cancer Genome Atlas (TCGA), RT-qPCR, Western blotting, and immunohistochemical analysis. The impact of IGF2BP1 on HNSCC cell proliferation was assessed through CCK-8 assay, plate cloning, and EdU assays. Cell motility was examined by Transwell migration and invasion assays. A tumor lymph node metastasis model in nude mice was established to evaluate the role of IGF2BP1 in lymphatic metastasis. Additionally, the regulatory effects of IGF2BP1 on the epithelial-mesenchymal transition (EMT) and the PI3K/AKT/mTOR signaling pathways were investigated using immunofluorescence and Western blotting. RESULTS: IGF2BP1 expression was significantly elevated in HNSCC tissues compared to adjacent normal tissues and was strongly associated with lymph node metastasis and poor prognosis. Knockdown of IGF2BP1 suppressed the proliferation, migration, and invasion of HNSCC cells. Furthermore, IGF2BP1 knockdown inhibited tumor growth and lymphatic metastasis in vivo. Mechanistically, IGF2BP1 was found to promote the EMT process by activating the PI3K/AKT/mTOR pathway, thereby enhancing the migratory and invasive capabilities of HNSCC cells. CONCLUSIONS: Our findings demonstrate that IGF2BP1 plays a critical role in promoting HNSCC growth and metastasis, highlighting its potential as a therapeutic target.