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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01201

CPT1A/2-mediated FAO Enhancement- A Metabolic Target in Radioresistant Breast Cancer

 Shujun Han1,  Ryan Wei2,  Nian Jiang3,  Ming Fan3, Bowen Xie3, Lu Zhang3,  Wieli Miao4,  Ashley Chen-Ping Butler3, Matthew A. Coleman3, Andrew T. Vaughan3, Yinsheng Wang4, Hong-Wu Chen5, Jiankang Liu1 and  Jian Jian Li3*
  • 1Xi'an Jiaotong University, China
  • 2Lewis Katz School of Medicine, Temple University, United States
  • 3Department of Radiation Oncology, University of California at Davis, United States
  • 4Department of Chemistry, University of California, Riverside, United States
  • 5Comprehensive Cancer Center, University of California, Davis, United States

Tumor cells including cancer stem cells (CSCs) resistant to radio- and chemo-therapy must enhance metabolism to meet the extra energy demands to repair and survive such genotoxic conditions. However, such stress-induced adaptive metabolic alternations, especially in cancer cells that survive radiotherapy, remains unresolved. In this study, we found that CPT1 (Carnitine palmitoyl transferase I) and CPT2 (Carnitine palmitoyl transferase II), a pair of rate-limiting enzymes for mitochondrial fatty acid transportation, play a critical role in increasing fatty acid oxidation (FAO) required for the cellular fuel demands in radioresistant breast cancer cells (RBCs) and radiation-derived breast cancer stem cells (RD-BCSCs). Enhanced CPT1A/CPT2 expression was detected in the recurrent human breast cancers and associated with a worse prognosis in breast cancer patients. Blocking FAO via FAO inhibitor or by CRISPR-mediated CPT1A/CPT2 gene deficiency inhibited radiation-induced ERK activation and aggressive growth and radioresistance of RBCs and RD-BCSCs. These results revealed that switching to FAO contributes to radiation-induced mitochondrial energy metabolism, and CPT1A/CPT2 is a potential metabolic target in cancer radiotherapy.

Keywords: Breast cancer stem cells, CPT1A/CPT2 , FAO metabolism, radioresistance, breast cancer

Received: 17 Apr 2019; Accepted: 22 Oct 2019.

Copyright: © 2019 Han, Wei, Jiang, Fan, Xie, Zhang, Miao, Butler, Coleman, Vaughan, Wang, Chen, Liu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jian Jian Li, Department of Radiation Oncology, University of California at Davis, Sacramento, 95817, California, United States, jijli@ucdavis.edu