PMID- 30945396
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20210503
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 110
IP  - 6
DP  - 2019 Jun
TI  - PGC1alpha/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma 
      through activating fatty acid oxidation.
PG  - 2050-2062
LID - 10.1111/cas.14011 [doi]
AB  - The PPAR coactivator-1alpha (PGC1alpha) is an important transcriptional co-activator in 
      control of fatty acid metabolism. Mitochondrial fatty acid oxidation (FAO) is the 
      primary pathway for the degradation of fatty acids and promotes NADPH and ATP 
      production. Our previous study demonstrated that upregulation of carnitine 
      palmitoyl transferase 1 A (CPT1A), the key regulator of FAO, promotes radiation 
      resistance of nasopharyngeal carcinoma (NPC). In this study, we found that high 
      expression of PGC1alpha is associated with poor overall survival in NPC patients 
      after radiation treatment. Targeting PGC1alpha could sensitize NPC cells to 
      radiotherapy. Mechanically, PGC1alpha binds to CCAAT/enhancer binding protein beta 
      (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A 
      transcription, resulting in activation of FAO. Our results revealed that the 
      PGC1alpha/CEBPB/CPT1A/FAO signaling axis promotes radiation resistance of NPC. These 
      findings indicate that the expression of PGC1alpha could be a prognostic indicator of 
      NPC, and targeting FAO in NPC with high expression of PGC1alpha might improve the 
      therapeutic efficacy of radiotherapy.
CI  - (c) 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd 
      on behalf of Japanese Cancer Association.
FAU - Du, Qianqian
AU  - Du Q
AUID- ORCID: 0000-0002-6729-3165
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
FAU - Tan, Zheqiong
AU  - Tan Z
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
FAU - Shi, Feng
AU  - Shi F
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
FAU - Tang, Min
AU  - Tang M
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
FAU - Xie, Longlong
AU  - Xie L
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
FAU - Zhao, Lin
AU  - Zhao L
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
FAU - Li, Yueshuo
AU  - Li Y
AUID- ORCID: 0000-0002-1680-915X
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
FAU - Hu, Jianmin
AU  - Hu J
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
FAU - Zhou, Min
AU  - Zhou M
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
FAU - Bode, Ann
AU  - Bode A
AD  - The Hormel Institute, University of Minnesota, Austin, Minnesota.
FAU - Luo, Xiangjian
AU  - Luo X
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
AD  - Molecular Imaging Research Center of Central South University, Changsha, China.
FAU - Cao, Ya
AU  - Cao Y
AD  - Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, 
      Xiangya Hospital, Central South University, Changsha, China.
AD  - Cancer Research Institute School of Basic Medicine Science, Xiangya School of 
      Medicine, Central South University, Changsha, China.
AD  - Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
AD  - Molecular Imaging Research Center of Central South University, Changsha, China.
AD  - Research Center for Technologies of Nucleic Acid-Based Diagnostics and 
      Therapeutics Hunan Province, Changsha, China.
AD  - National Joint Engineering Research Center for Genetic Diagnostics of Infectious 
      Diseases and Cancer, Changsha, China.
LA  - eng
GR  - HN2016-01/Open Projects of State Key Laboratory Of Oncology In South China/
GR  - 81573014/National Natural Science Foundation of China/
GR  - 81874195/National Natural Science Foundation of China/
GR  - 2018SK2123/Key Projects of Key Research and Development Program of Hunan 
      Province/
PT  - Journal Article
DEP - 20190503
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (CEBPB protein, human)
RN  - 0 (Fatty Acids)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - EC 2.3.1.21 (CPT1A protein, human)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
SB  - IM
MH  - CCAAT-Enhancer-Binding Protein-beta/*genetics/metabolism
MH  - Carnitine O-Palmitoyltransferase/*genetics/metabolism
MH  - Cell Line, Tumor
MH  - Fatty Acids/*metabolism
MH  - Gene Expression Regulation, Neoplastic/radiation effects
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Nasopharyngeal Carcinoma/genetics/metabolism/*radiotherapy
MH  - Nasopharyngeal Neoplasms/genetics/metabolism/*radiotherapy
MH  - Oxidation-Reduction/radiation effects
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 
      1-alpha/*genetics/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding/radiation effects
MH  - RNA Interference
PMC - PMC6550130
OTO - NOTNLM
OT  - CPT1A
OT  - PGC1alpha
OT  - fatty acid oxidation
OT  - nasopharyngeal carcinoma
OT  - radiation therapy
EDAT- 2019/04/05 06:00
MHDA- 2019/06/25 06:00
PMCR- 2019/06/01
CRDT- 2019/04/05 06:00
PHST- 2019/01/24 00:00 [received]
PHST- 2019/03/29 00:00 [revised]
PHST- 2019/04/01 00:00 [accepted]
PHST- 2019/04/05 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
PHST- 2019/04/05 06:00 [entrez]
PHST- 2019/06/01 00:00 [pmc-release]
AID - CAS14011 [pii]
AID - 10.1111/cas.14011 [doi]
PST - ppublish
SO  - Cancer Sci. 2019 Jun;110(6):2050-2062. doi: 10.1111/cas.14011. Epub 2019 May 3.