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.

Details

Title
CPT1A-mediated fatty acid oxidation promotes cell proliferation via nucleoside metabolism in nasopharyngeal carcinoma
Author
Tang, Min 1 ; Dong, Xin 2 ; Xiao Lanbo 3 ; Tan Zheqiong 3 ; Luo Xiangjian 1 ; Yang, Lifang 1 ; Li, Wei 3 ; Shi, Feng 3 ; Li Yueshuo 3 ; Zhao, Lin 3 ; Liu, Na 3 ; Du Qianqian 3 ; Xie Longlong 3 ; Hu, Jianmin 3 ; Weng Xinxian 3 ; Fan, Jia 4   VIAFID ORCID Logo  ; Zhou, Jian 4   VIAFID ORCID Logo  ; Gao Qiang 4   VIAFID ORCID Logo  ; Wu, Weizhong 4 ; Zhang, Xin 5 ; Liao Weihua 6 ; Bode, Ann M 7 ; Cao Ya 8   VIAFID ORCID Logo 

1  Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, Cancer Research Institute and School of Basic Medical Science, Xiangya School of Medicine, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Chinese Ministry of Health, Key Laboratory of Carcinogenesis, Changsha, China (GRID:grid.216417.7); Molecular Imaging Research Center of Central South University, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
2  Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, Cancer Research Institute and School of Basic Medical Science, Xiangya School of Medicine, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Chinese Ministry of Health, Key Laboratory of Carcinogenesis, Changsha, China (GRID:grid.216417.7); Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Laboratory, National Cancer Center / National Clinical Research Center for Cancer/Cancer Hospital, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839) 
3  Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, Cancer Research Institute and School of Basic Medical Science, Xiangya School of Medicine, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Chinese Ministry of Health, Key Laboratory of Carcinogenesis, Changsha, China (GRID:grid.216417.7) 
4  Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Zhongshan Hospital, Shanghai Medical School, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
5  Central South University, Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
6  Molecular Imaging Research Center of Central South University, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, Department of Radiology, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
7  University of Minnesota, The Hormel Institute, Austin, USA (GRID:grid.17635.36) (ISNI:0000000419368657) 
8  Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, Cancer Research Institute and School of Basic Medical Science, Xiangya School of Medicine, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Chinese Ministry of Health, Key Laboratory of Carcinogenesis, Changsha, China (GRID:grid.216417.7); Molecular Imaging Research Center of Central South University, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Research Center for Technologies of Nucleic Acid-Based Diagnostics and Therapeutics Hunan Province, Changsha, China (GRID:grid.216417.7); National Joint Engineering Research Center for Genetic Diagnostics of Infectious Diseases and Cancer, Changsha, China (GRID:grid.216417.7); Central South University, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
Publication year
2022
Publication date
Apr 2022
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-022-04730-y
ProQuest document ID
2649217140
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.