Open AccessPGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation
Author(s) -
Du Qianqian,
Tan Zheqiong,
Shi Feng,
Tang Min,
Xie Longlong,
Zhao Lin,
Li Yueshuo,
Hu Jianmin,
Zhou Min,
Bode Ann,
Luo Xiangjian,
Cao Ya
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14011
Subject(s) - downregulation and upregulation , nasopharyngeal carcinoma , beta oxidation , coactivator , cancer research , transcription factor , carnitine , biology , peroxisome proliferator activated receptor , medicine , radiation therapy , endocrinology , metabolism , biochemistry , gene
The PPAR coactivator‐1α (PGC1α) 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 PGC1α is associated with poor overall survival in NPC patients after radiation treatment. Targeting PGC1α could sensitize NPC cells to radiotherapy. Mechanically, PGC1α binds to CCAAT/enhancer binding protein β (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Our results revealed that the PGC1α/CEBPB/CPT1A/FAO signaling axis promotes radiation resistance of NPC. These findings indicate that the expression of PGC1α could be a prognostic indicator of NPC, and targeting FAO in NPC with high expression of PGC1α might improve the therapeutic efficacy of radiotherapy.