The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression.

ABSTRACT: The transcription factor NRF2 is the major mediator of oxidative stress responses and is closely connected to therapy resistance in tumors harboring activating mutations in the NRF2 pathway. In melanoma, such mutations are rare, and it is unclear to what extent melanomas rely on NRF2. Here we show that NRF2 suppresses the activity of the melanocyte lineage marker MITF in melanoma, thereby reducing the expression of pigmentation markers. Intriguingly, we furthermore identified NRF2 as key regulator of immune-modulating genes, linking oxidative stress with the induction of cyclooxygenase 2 (COX2) in an ATF4-dependent manner. COX2 is critical for the secretion of prostaglandin E2 and was strongly induced by H₂O₂ or TNFα only in presence of NRF2. Induction of MITF and dep

SUBMITTER: Jessen C 

PROVIDER: S-EPMC7605435 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature