Inducible mucosa-like differentiation of head and neck cancer cells drives the epigenetically determined loss of cell malignancy

Human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease with high death rates that have remained substantially unaltered for decades. Therefore, new treatment approaches are urgently needed. Human papillomavirus-negative tumors harbor areas of terminally differentiated tissue that are characterized by cornification. Dissecting this intrinsic ability of HNSCC cells to irreversibly differentiate into non-malignant cells may have striking tumor-targeting potential. Primary head and neck squamous cell carcinoma cell cultures were established in a serum-free medium to investigate the differentiation potential of HNSCC. The cells were differentiated with a serum medium and cultured for 8 days until full differentiation was achieved. Both cultures under the control condition (PNEU) and the differentiation condition (CFM) have been analyzed using ATAC-seq.