Author:
Xu Iris Ming-Jing,Lai Robin Kit-Ho,Lin Shu-Hai,Tse Aki Pui-Wah,Chiu David Kung-Chun,Koh Hui-Yu,Law Cheuk-Ting,Wong Chun-Ming,Cai Zongwei,Wong Carmen Chak-Lui,Ng Irene Oi-Lin
Abstract
Cancer cells experience an increase in oxidative stress. The pentose phosphate pathway (PPP) is a major biochemical pathway that generates antioxidant NADPH. Here, we show that transketolase (TKT), an enzyme in the PPP, is required for cancer growth because of its ability to affect the production of NAPDH to counteract oxidative stress. We show that TKT expression is tightly regulated by the Nuclear Factor, Erythroid 2-Like 2 (NRF2)/Kelch-Like ECH-Associated Protein 1 (KEAP1)/BTB and CNC Homolog 1 (BACH1) oxidative stress sensor pathway in cancers. Disturbing the redox homeostasis of cancer cells by genetic knockdown or pharmacologic inhibition of TKT sensitizes cancer cells to existing targeted therapy (Sorafenib). Our study strengthens the notion that antioxidants are beneficial to cancer growth and highlights the therapeutic benefits of targeting pathways that generate antioxidants.
Funder
Health and Medican Research Fund
National Natural Science Foundation of China
Hong Kong Research Grant Council Collaborative Research Fund
Publisher
Proceedings of the National Academy of Sciences
Cited by
177 articles.
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