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

Shujun Han, Ryan Wei, Xiaodi Zhang, Nian Jiang, Ming Fan, Jie Hunter Huang, Bowen Xie, Lu Zhang, Weili Miao, Ashley Chen Ping Butler, Matthew A. Coleman, Andrew T. Vaughan, Yinsheng Wang, Hong Wu Chen, Jiankang Liu, Jian Jian Li

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Tumor cells, including cancer stem cells (CSCs) resistant to radio- and chemotherapy, must enhance metabolism to meet the extra energy demands to repair and survive such genotoxic conditions. However, such stress-induced adaptive metabolic alterations, especially in cancer cells that survive radiotherapy, remain 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 a 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.

Original languageEnglish (US)
Article number1201
JournalFrontiers in Oncology
Volume9
DOIs
StatePublished - Nov 15 2019

Keywords

  • breast cancer
  • breast cancer stem cells
  • CPT1A/CPT2
  • FAO
  • metabolism
  • radioresistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Han, S., Wei, R., Zhang, X., Jiang, N., Fan, M., Huang, J. H., Xie, B., Zhang, L., Miao, W., Butler, A. C. P., Coleman, M. A., Vaughan, A. T., Wang, Y., Chen, H. W., Liu, J., & Li, J. J. (2019). CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer. Frontiers in Oncology, 9, [1201]. https://doi.org/10.3389/fonc.2019.01201