Abstract

Anoikis is a critical obstacle to cancer metastasis. Colorectal cancer (CRC) exhibits a high rate of metastasis, leading to death, and the mechanisms involved in anoikis resistance are still unclear. We identified that the fatty acid oxidation (FAO) pathway was activated in detached CRC cells. Multiple genes in the FAO pathway, specifically the rate-limiting enzyme CPT1A, were upregulated in CRC cells grown in suspension. Reactive oxygen species elimination mediated by CPT1A in CRC cells was vital to anoikis resistance. In vivo experiments showed that CPT1A-suppressed CRC cells colonized the lung at a much lower rate than normal CRC cells, suggesting that CPT1A-mediated FAO activation increased metastatic capacity. In clinical tissue specimens from CRC patients, elevated expression of CPT1A was observed in metastatic sites compared with primary sites. Our results demonstrate that CPT1A-mediated FAO activation induces CRC cells to resist anoikis, suggesting that CPT1A is an attractive target for treating metastatic CRC.

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Acknowledgements

This research was supported by the National Natural Science Foundation of China (81602137, 81572392); Natural Science Foundation of Guangdong Province (2017A030313485, 2014A030312015); Science and Technology Program of Guangdong (2015B020232008), Science and Technology Program of Guangzhou (15570006, 201508020250, 201604020003) and by grants from Pearl River S&T Nova Program of Guangzhou (201806010002).

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Author notes

  1. These authors contributed equally: Ying-nan Wang, Zhao-lei Zeng, Jiahuan Lu

Affiliations

  1. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 510060, Guangzhou, China

    • Ying-nan Wang
    • , Zhao-lei Zeng
    • , Jiahuan Lu
    • , Yun Wang
    • , Ze-xian Liu
    • , Ming-ming He
    • , Qi Zhao
    • , Zi-xian Wang
    • , Ting Li
    • , Yun-xin Lu
    • , Qi-nian Wu
    • , Kai Yu
    • , Feng Wang
    • , Heng-Ying Pu
    • , Wei-hua Jia
    • , Ming shi
    • , Dan Xie
    • , Tie-bang Kang
    • , Huai-qiang Ju
    •  & Rui-hua Xu
  2. Department of Biochemistry and Molecular Biology, Zhongshan School of Medicine, Sun Yat-Sen University, 510080, Guangzhou, China

    • Bo Li
  3. Departments of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    • Peng Huang

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https://doi.org/10.1038/s41388-018-0384-z