Transketolase counteracts oxidative stress to drive cancer development.

Autor:	Xu IM; Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;, Lai RK; Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;, Lin SH; Department of Chemistry,Hong Kong Baptist University, Hong Kong, SAR, China; State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong, SAR, China;, Tse AP; Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;, Chiu DK; Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;, Koh HY; Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;, Law CT; Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;, Wong CM; Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, SAR, China., Cai Z; Department of Chemistry,Hong Kong Baptist University, Hong Kong, SAR, China; State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong, SAR, China;, Wong CC; Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, SAR, China iolng@hku.hk carmencl@pathology.hku.hk., Ng IO; Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, SAR, China iolng@hku.hk carmencl@pathology.hku.hk.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2016 Feb 09; Vol. 113 (6), pp. E725-34. Date of Electronic Publication: 2016 Jan 25.
DOI:	10.1073/pnas.1508779113
Abstrakt:	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.
Databáze:	MEDLINE
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