PMID- 26811478
OWN - NLM
STAT- MEDLINE
DCOM- 20160704
LR  - 20220311
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 113
IP  - 6
DP  - 2016 Feb 9
TI  - Transketolase counteracts oxidative stress to drive cancer development.
PG  - E725-34
LID - 10.1073/pnas.1508779113 [doi]
AB  - 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.
FAU - Xu, Iris Ming-Jing
AU  - Xu IM
AD  - Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;
FAU - Lai, Robin Kit-Ho
AU  - Lai RK
AD  - Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;
FAU - Lin, Shu-Hai
AU  - Lin SH
AD  - 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;
FAU - Tse, Aki Pui-Wah
AU  - Tse AP
AD  - Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;
FAU - Chiu, David Kung-Chun
AU  - Chiu DK
AD  - Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;
FAU - Koh, Hui-Yu
AU  - Koh HY
AD  - Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;
FAU - Law, Cheuk-Ting
AU  - Law CT
AD  - Department of Pathology, The University of Hong Kong, Hong Kong, SAR, China;
FAU - Wong, Chun-Ming
AU  - Wong CM
AD  - 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.
FAU - Cai, Zongwei
AU  - Cai Z
AD  - 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;
FAU - Wong, Carmen Chak-Lui
AU  - Wong CC
AD  - 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.
FAU - Ng, Irene Oi-Lin
AU  - Ng IO
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160125
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Peroxides)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - EC 2.2.1.1 (Transketolase)
RN  - GAN16C9B8O (Glutathione)
RN  - IY9XDZ35W2 (Glucose)
RN  - M7ZJ88F4R1 (tert-butyl peroxide)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Carcinoma, Hepatocellular/*enzymology/*pathology
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Glucose/metabolism
MH  - Glutathione/metabolism
MH  - Glycolysis/drug effects
MH  - Humans
MH  - Liver Neoplasms/enzymology/pathology
MH  - Male
MH  - Metabolome/drug effects
MH  - Mice, Nude
MH  - Molecular Sequence Data
MH  - Niacinamide/analogs & derivatives/pharmacology
MH  - *Oxidative Stress/drug effects
MH  - Pentose Phosphate Pathway/drug effects
MH  - Peroxides/pharmacology
MH  - Phenylurea Compounds/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Sorafenib
MH  - Transketolase/antagonists & inhibitors/genetics/*metabolism
MH  - Up-Regulation/drug effects
PMC - PMC4760787
OTO - NOTNLM
OT  - HCC
OT  - PPP
OT  - ROS
OT  - TKT
OT  - metabolism
COIS- The authors declare no conflict of interest.
EDAT- 2016/01/27 06:00
MHDA- 2016/07/05 06:00
PMCR- 2016/01/25
CRDT- 2016/01/27 06:00
PHST- 2016/01/27 06:00 [entrez]
PHST- 2016/01/27 06:00 [pubmed]
PHST- 2016/07/05 06:00 [medline]
PHST- 2016/01/25 00:00 [pmc-release]
AID - 1508779113 [pii]
AID - 201508779 [pii]
AID - 10.1073/pnas.1508779113 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2016 Feb 9;113(6):E725-34. doi: 
      10.1073/pnas.1508779113. Epub 2016 Jan 25.