NRF2 activation induces NADH-reductive stress, providing a metabolic vulnerability in lung cancer.
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ABSTRACT:
SUBMITTER: Weiss-Sadan T
PROVIDER: S-EPMC9998367 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
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NRF2 activation induces NADH-reductive stress, providing a metabolic vulnerability in lung cancer.
Weiss-Sadan Tommy T Ge Maolin M Hayashi Makiko M Gohar Magdy M Yao Cong-Hui CH de Groot Adriaan A Harry Stefan S Carlin Alexander A Fischer Hannah H Shi Lei L Wei Ting-Yu TY Adelmann Charles H CH Wolf Konstantin K Vornbäumen Tristan T Dürr Benedikt R BR Takahashi Mariko M Richter Marianne M Zhang Junbing J Yang Tzu-Yi TY Vijay Vindhya V Fisher David E DE Hata Aaron N AN Haigis Marcia C MC Mostoslavsky Raul R Bardeesy Nabeel N Papagiannakopoulos Thales T Bar-Peled Liron L
Cell metabolism 20230224 3
Multiple cancers regulate oxidative stress by activating the transcription factor NRF2 through mutation of its negative regulator, KEAP1. NRF2 has been studied extensively in KEAP1-mutant cancers; however, the role of this pathway in cancers with wild-type KEAP1 remains poorly understood. To answer this question, we induced NRF2 via pharmacological inactivation of KEAP1 in a panel of 50+ non-small cell lung cancer cell lines. Unexpectedly, marked decreases in viability were observed in >13% of t ...[more]
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