Pluripotency transcription factor Nanog and its association with overall oral squamous cell carcinoma progression, cisplatin‐resistance, invasion and stemness acquisition

Background Cisplatin‐resistant oral squamous cell carcinoma (OSCC) cells acquire stem‐like characteristics and are difficult to treat. Nanog is a transcription factor and needed for maintenance of pluripotency, but its transcription‐promoting role in OSCC progression and cisplatin resistance is poorly understood. Methods Here, 110 fresh human tissue specimens of various stages, including invasive (N1‐3)/chemoradiation‐resistant OSCC samples, cisplatin‐resistant (CisR‐SCC‐4/‐9) OSCC cells/parental cells, photochemical ECGC, and siRNA (Nanog) were used. Results Nanog overexpression was associated with overall progression, chemoresistance, and invasion of OSCC. Nanog recruitment to c‐Myc, Slug, E‐cadherin, and Oct‐4 gene promoter was observed. Positive correlation of Nanog protein expression with c‐Myc, Slug, cyclin D1, MMP‐2/‐9, and Oct‐4 and negative correlation with E‐cadherin gene expression were found. Knockdown of Nanog and treatment of epicatechin‐3‐gallate reversed cisplatin resistance and diminished invasion/migration potential. Conclusion Nanog directly participated in the regulation of Slug, E‐cadherin, Oct‐4, and c‐Myc genes, causing cisplatin resistance/recurrence of OSCC.