Our finding that the inhibition of NRF2 expression (by siRNA knockdown or the NRF2-specific inhibitor ML385) significantly reduces CD109-mediated IL-6-dependent stemness in SCC cells, support a unique model where the CD109/IL6Rα/STAT3/NRF2 axis plays a critical role in promoting cancer cell stemness. The gene discussed is CD109; the disease is cancer.