Fig. 8

Schematic diagram of TNFAIP2 confers cisplatin resistance by sustaining NRF2 signaling activation in HNSCC. In cancer cells, highly expressed TNFAIP2 interacts with KEAP1, which protects NRF2 from ubiquitin proteasome-mediated degradation. Accumulated NRF2 occurs the nuclear translocation and promotes the transcription of antioxidant genes. These genes could efficiently scavenge ROS, which accumulate upon cisplatin treatment, thereby inhibiting the phosphorylation of JNK as well as the activation of its downstream apoptosis pathway. The above mechanism ultimately results in cisplatin treatment resistance in HNSCC patients with upregulation of TNFAIP2.