Nrf2, YAP, antioxidant potential, and cancer

The antioxidant response is principally mediated by the transcription factor Nrf2 that can induce the expression of genes involved in xenobiotic detoxification and cytoprotection. Several reports indicate the involvement of Nrf2 in cancer progression and chemoresistance. The transcriptional coactivator YAP, belonging to the Hippo pathway, is often deregulated in cancer, contributing to cancer cell growth, progression, and chemoresistance. Moreover, recent findings reveal that it is also involved in oxidative stress. Indeed, it has been found that Nrf2 and YAP can cooperate in maintaining the antioxidant status. Moreover, cross talk between YAP and Nrf2 was also demonstrated: Nrf2 can indirectly induce the transcription of YAP and YAP can indirectly induce Nrf2 expression.Both genes seem to be good candidates as targets in anticancer therapies: the inhibition of Nrf2 or YAP alone increases the sensitivity to prooxidant chemotherapeutic drugs, such as cisplatin, through the induction of oxidative stress; moreover, their contemporary inhibition further enhances the sensitivity to cisplatin. New preclinical and clinical studies would allow the identification of more specific Nrf2 or YAP inhibitors. Drugs, such as the natural compound ailanthone, capable of inhibiting both molecules, are worthy of attention from the scientists.