SOX2 and lip and oral cavity carcinoma: Other stemness markers, such as CD44, CD133, glucose-regulated protein 78 (Grp-78), Grp-96, Oct-4, Nanog and SOX2, are upregulated upon exposure to areca nut and correlate with worse prognosis in areca nut-induced cancers.49,50 Furthermore, areca nut-induced chemoradioresistance results from the upregulation of ATP-binding cassette subfamily G member-2 (ABCG-2), a drug- efflux pump and a stem cell marker.22,49,50 Oral cancers among habitual areca nut chewers demonstrate an aggressive phenotype, chemoradioresistance and a much lower 5-year survival rate than those without areca habits.18