CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer
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 radioth...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-11-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.01201/full |
| id |
doaj-6489abd152a440d0bf890a215853fcc2 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Shujun Han Shujun Han Ryan Wei Ryan Wei Xiaodi Zhang Nian Jiang Ming Fan Jie Hunter Huang Bowen Xie Lu Zhang Weili Miao Ashley Chen-Ping Butler Matthew A. Coleman Matthew A. Coleman Andrew T. Vaughan Andrew T. Vaughan Yinsheng Wang Hong-Wu Chen Hong-Wu Chen Jiankang Liu Jian Jian Li Jian Jian Li |
| spellingShingle |
Shujun Han Shujun Han Ryan Wei Ryan Wei Xiaodi Zhang Nian Jiang Ming Fan Jie Hunter Huang Bowen Xie Lu Zhang Weili Miao Ashley Chen-Ping Butler Matthew A. Coleman Matthew A. Coleman Andrew T. Vaughan Andrew T. Vaughan Yinsheng Wang Hong-Wu Chen Hong-Wu Chen Jiankang Liu Jian Jian Li Jian Jian Li CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer Frontiers in Oncology breast cancer stem cells CPT1A/CPT2 FAO metabolism radioresistance breast cancer |
| author_facet |
Shujun Han Shujun Han Ryan Wei Ryan Wei Xiaodi Zhang Nian Jiang Ming Fan Jie Hunter Huang Bowen Xie Lu Zhang Weili Miao Ashley Chen-Ping Butler Matthew A. Coleman Matthew A. Coleman Andrew T. Vaughan Andrew T. Vaughan Yinsheng Wang Hong-Wu Chen Hong-Wu Chen Jiankang Liu Jian Jian Li Jian Jian Li |
| author_sort |
Shujun Han |
| title |
CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer |
| title_short |
CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer |
| title_full |
CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer |
| title_fullStr |
CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer |
| title_full_unstemmed |
CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer |
| title_sort |
cpt1a/2-mediated fao enhancement—a metabolic target in radioresistant breast cancer |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Oncology |
| issn |
2234-943X |
| publishDate |
2019-11-01 |
| description |
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. |
| topic |
breast cancer stem cells CPT1A/CPT2 FAO metabolism radioresistance breast cancer |
| url |
https://www.frontiersin.org/article/10.3389/fonc.2019.01201/full |
| work_keys_str_mv |
AT shujunhan cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT shujunhan cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT ryanwei cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT ryanwei cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT xiaodizhang cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT nianjiang cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT mingfan cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT jiehunterhuang cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT bowenxie cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT luzhang cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT weilimiao cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT ashleychenpingbutler cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT matthewacoleman cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT matthewacoleman cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT andrewtvaughan cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT andrewtvaughan cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT yinshengwang cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT hongwuchen cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT hongwuchen cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT jiankangliu cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT jianjianli cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer AT jianjianli cpt1a2mediatedfaoenhancementametabolictargetinradioresistantbreastcancer |
| _version_ |
1724902231827808256 |
| spelling |
doaj-6489abd152a440d0bf890a215853fcc22020-11-25T02:14:03ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-11-01910.3389/fonc.2019.01201464430CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast CancerShujun Han0Shujun Han1Ryan Wei2Ryan Wei3Xiaodi Zhang4Nian Jiang5Ming Fan6Jie Hunter Huang7Bowen Xie8Lu Zhang9Weili Miao10Ashley Chen-Ping Butler11Matthew A. Coleman12Matthew A. Coleman13Andrew T. Vaughan14Andrew T. Vaughan15Yinsheng Wang16Hong-Wu Chen17Hong-Wu Chen18Jiankang Liu19Jian Jian Li20Jian Jian Li21Department of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesCenter for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, ChinaDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesLewis Katz School of Medicine/St. Luke's University Regional Campus, Temple University, Philadelphia, PA, United StatesDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesDepartment of Chemistry, University of California, Riverside, Riverside, CA, United StatesDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesNCI-Designated Compressive Cancer Center, School of Medicine, University of California, Davis, Sacramento, CA, United StatesDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesNCI-Designated Compressive Cancer Center, School of Medicine, University of California, Davis, Sacramento, CA, United StatesDepartment of Chemistry, University of California, Riverside, Riverside, CA, United StatesNCI-Designated Compressive Cancer Center, School of Medicine, University of California, Davis, Sacramento, CA, United StatesDepartment of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA, United StatesCenter for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, ChinaDepartment of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesNCI-Designated Compressive Cancer Center, School of Medicine, University of California, Davis, Sacramento, CA, United StatesTumor 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.https://www.frontiersin.org/article/10.3389/fonc.2019.01201/fullbreast cancer stem cellsCPT1A/CPT2FAOmetabolismradioresistancebreast cancer |