Transketolase counteracts oxidative stress to drive cancer development

IMJ Xu, RKH Lai, SH Lin, APW Tse… - Proceedings of the …, 2016 - National Acad Sciences
IMJ Xu, RKH Lai, SH Lin, APW Tse, DKC Chiu, HY Koh, CT Law, CM Wong, Z Cai…
Proceedings of the National Academy of Sciences, 2016National Acad Sciences
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 …
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.
National Acad Sciences