Induction of c-Myc-dependent cell proliferation through toll-like receptor 3 in head and neck cancer

Protein expression of human toll-like receptors (TLR) 1-10 was measured in cell lines and solid tumors of head and neck squamous cell carcinoma (HNSCC). All HNSCC cell lines and 80% of solid tumors were found to express TLR3 as a predominantly intracellular protein, while no other TLR proteins were expressed. TLR3 has previously been shown to contribute to the activation of nuclear factor-κB (NF-κB), a transcription factor which promotes several types of human cancers. Significantly, NF-κB expression was strongest in protein extracts from carcinoma tissue in which TLR3 was overexpressed. Inhibition of TLR3 expression in permanent HNSCC cell lines resulted in decreased expression of the oncoprotein c-Myc resulting in decreased cell proliferation. Correspondingly, overexpression of human TLR3 in mouse fibroblasts resulted in an upregulation of c-Myc and increased sensitivity for PolyI:C-induced cell proliferation. Our data suggest that TLR3 contributes to the malignant phenotype leading to invasive carcinoma in HNSCC.