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

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

Fingerprint

Fatty Acids
Breast Neoplasms
Neoplastic Stem Cells
Radiation
Radiotherapy
Carnitine
Transferases
Clustered Regularly Interspaced Short Palindromic Repeats
Neoplasms
Energy Metabolism
Drug Therapy
Enzymes
Growth
Genes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Han, S., Wei, R., Zhang, X., Jiang, N., Fan, M., Huang, J. H., ... 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

CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer. / Han, Shujun; Wei, Ryan; Zhang, Xiaodi; Jiang, Nian; Fan, Ming; Huang, Jie Hunter; Xie, Bowen; Zhang, Lu; Miao, Weili; Butler, Ashley Chen Ping; Coleman, Matthew A.; Vaughan, Andrew T.; Wang, Yinsheng; Chen, Hong Wu; Liu, Jiankang; Li, Jian Jian.

In: Frontiers in Oncology, Vol. 9, 1201, 15.11.2019.

Research output: Contribution to journalArticle

Han, S, Wei, R, Zhang, X, Jiang, N, Fan, M, Huang, JH, Xie, B, Zhang, L, Miao, W, Butler, ACP, Coleman, MA, Vaughan, AT, Wang, Y, Chen, HW, Liu, J & Li, JJ 2019, 'CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer', Frontiers in Oncology, vol. 9, 1201. https://doi.org/10.3389/fonc.2019.01201
Han, Shujun ; Wei, Ryan ; Zhang, Xiaodi ; Jiang, Nian ; Fan, Ming ; Huang, Jie Hunter ; Xie, Bowen ; Zhang, Lu ; Miao, Weili ; Butler, Ashley Chen Ping ; Coleman, Matthew A. ; Vaughan, Andrew T. ; Wang, Yinsheng ; Chen, Hong Wu ; Liu, Jiankang ; Li, Jian Jian. / CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer. In: Frontiers in Oncology. 2019 ; Vol. 9.
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AU - Butler, Ashley Chen Ping

AU - Coleman, Matthew A.

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