PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation

Qianqian Du, Zheqiong Tan, Feng Shi, Min Tang, Longlong Xie, Lin Zhao, Yueshuo Li, Jianmin Hu, Min Zhou, Ann Bode, Xiangjian Luo, Ya Cao

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2050-2062
Number of pages13
JournalCancer Science
Volume110
Issue number6
DOIs
StatePublished - Jun 2019

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (No. 81573014, 81874195); Open Projects of State Key Laboratory of Oncology in South China (HN2016-01); Key Projects of Key Research and Development Program of Hunan Province (2018SK2123).

Publisher Copyright:
© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Keywords

  • CPT1A
  • PGC1α
  • fatty acid oxidation
  • nasopharyngeal carcinoma
  • radiation therapy

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