Transketolase counteracts oxidative stress to drive cancer development

Iris Ming Jing Xu, Robin Kit Ho Lai, Shuhai LIN, Aki Pui Wah Tse, David Kung Chun Chiu, Hui Yu Koh, Cheuk Ting Law, Chun Ming Wong, Zongwei CAI, Carmen Chak Lui Wong*, Irene Oi Lin Ng

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)

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 ECHAssociated 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.

Original languageEnglish
Pages (from-to)E725-E734
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number6
DOIs
Publication statusPublished - 9 Feb 2016

Scopus Subject Areas

  • General

User-Defined Keywords

  • HCC
  • Metabolism
  • PPP
  • ROS
  • TKT

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