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Cell Death Dis. 2022 Apr 11;13(4):331.doi: 10.1038/s41419-022-04730-y.

CPT1A-mediated fatty acid oxidation promotes cell proliferation via nucleoside metabolism in nasopharyngeal carcinoma.

Min Tang 1,2,3,4, Xin Dong 1,2,3,5, Lanbo Xiao 1,2,3, Zheqiong Tan 1,2,3, Xiangjian Luo 1,2,3,4, Lifang Yang 1,2,3,4, Wei Li 1,2,3, Feng Shi 1,2,3, Yueshuo Li 1,2,3, Lin Zhao 1,2,3, Na Liu 1,2,3, Qianqian Du 1,2,3, Longlong Xie 1,2,3, Jianmin Hu 1,2,3, Xinxian Weng 1,2,3, Jia Fan 6, Jian Zhou 6, Qiang Gao 6, Weizhong Wu 6, Xin Zhang 7, Weihua Liao 4,8, Ann M Bode 9, Ya Cao 10,11,12,13,14,15,16

Affiliations

  • 1 Key Laboratory of Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Central South University, 410078, Changsha, China.
  • 2 Cancer Research Institute and School of Basic Medical Science, Xiangya School of Medicine, Central South University, 410078, Changsha, China.
  • 3 Key Laboratory of Carcinogenesis, Chinese Ministry of Health, 410078, Changsha, China.
  • 4 Molecular Imaging Research Center of Central South University, 410008, Changsha, Hunan, China.
  • 5 Department of Laboratory, National Cancer Center / National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
  • 6 Key Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Zhongshan Hospital, Shanghai Medical School, Fudan University, 200000, Shanghai, China.
  • 7 Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 410078, Changsha, China.
  • 8 Department of Radiology, Xiangya Hospital, Central South University, 410078, Changsha, China.
  • 9 The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
  • 10 Key Laboratory of Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Central South University, 410078, Changsha, China. [email protected].
  • 11 Cancer Research Institute and School of Basic Medical Science, Xiangya School of Medicine, Central South University, 410078, Changsha, China. [email protected].
  • 12 Key Laboratory of Carcinogenesis, Chinese Ministry of Health, 410078, Changsha, China. [email protected].
  • 13 Molecular Imaging Research Center of Central South University, 410008, Changsha, Hunan, China. [email protected].
  • 14 Research Center for Technologies of Nucleic Acid-Based Diagnostics and Therapeutics Hunan Province, 410078, Changsha, China. [email protected].
  • 15 National Joint Engineering Research Center for Genetic Diagnostics of Infectious Diseases and Cancer, 410078, Changsha, China. [email protected].
  • 16 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 410078, Changsha, China. [email protected].

Abstract

As the first rate-limiting enzyme in fatty acid oxidation (FAO), CPT1 plays a significant role in metabolic adaptation in cancer pathogenesis. FAO provides an alternative energy supply for cancer cells and is required for cancer cell survival. Given the high proliferation rate of cancer cells, nucleotide synthesis gains prominence in rapidly proliferating cells. In the present study, we found that CPT1A is a determining factor for the abnormal activation of FAO in nasopharyngeal carcinoma (NPC) cells. CPT1A is highly expressed in NPC cells and biopsies. CPT1A dramatically affects the malignant phenotypes in NPC, including proliferation, anchorage-independent growth, and tumor formation ability in nude mice. Moreover, an increased level of CPT1A promotes core metabolic pathways to generate ATP, inducing equivalents and the main precursors for nucleotide biosynthesis. Knockdown of CPT1A markedly lowers the fraction of 13C-palmitate-derived carbons into pyrimidine. Periodic activation of CPT1A increases the content of nucleoside metabolic intermediates promoting cell cycle progression in NPC cells. Targeting CPT1A-mediated FAO hinders the cell cycle G1/S transition. Our work verified that CPT1A links FAO to cell cycle progression in NPC cellular proliferation, which supplements additional experimental evidence for developing a therapeutic mechanism based on manipulating lipid metabolism.

https://doi.org/10.1038/s41419-022-04730-y

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