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Nestin regulates proliferation and invasion of gastrointestinal stromal tumor cells by altering mitochondrial dynamics

Oncogene volume 35, pages 3139–3150 (2016)Cite this article

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Abstract

Nestin is widely expressed in numerous tumors and has become a diagnostic and prognostic indicator. However, the exact mechanism by which nestin contributes to tumor malignancy remains poorly understood. Here, we found marked upregulation of nestin expression in highly proliferative and invasive gastrointestinal stromal tumor (GIST) specimens. Nestin knockdown in GIST cells reduced the proliferative and invasive activity owing to a decrease of mitochondrial intracellular reactive oxygen species (ROS) generation. Furthermore, nestin was co-localized with mitochondria, and knockdown of nestin increased mitochondrial elongation and influenced the mitochondrial function, including oxygen consumption rates, ATP generation and mitochondrial membrane potential and so on. In exploring the underlying mechanism, we demonstrated nestin knockdown inhibited the mitochondrial recruitment of Dynamin-related protein1 and induced the change of mitochondrial dynamics. Thus, nestin may have an important role in GIST malignancy by regulating mitochondrial dynamics and altering intracellular ROS levels. The findings provide new clues to reveal mechanisms by which nestin mediates the proliferation and invasion of GISTs.

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Acknowledgements

This work was supported by the National Basic Research Program of China (2012CBA01302); the National Natural Science Foundation of China (81425016, 81270646, 31171398); the Natural Science Foundation of Guangdong Province (S2013030013305, 2015A030312013); the Key Scientific and Technological Projects of Guangdong Province (2014B020226002, 2015B020226004, 2014B020228003, 2007A032100003); Key Scientific and Technological Program of Guangzhou City (201400000003-3, 201508020262, 201300000089, 2010U1-E00551); Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (GDUPS, 2013).

Author contributions

JW, JC, YH, QK, BW, SW, YW, WL, and APX designed and performed experiments. XH analyzed results. JW, JC, YH, CL and APX assembled results and wrote the paper. TW, WS and WL provided tools, patient specimens and edited the manuscript. All authors participated in critical revision of the manuscript for important intellectual content.

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Author notes

  1. J Wang and J Cai: These authors contributed equally to this work.

Authors and Affiliations

  1. Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children’s Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

    J Wang, J Cai, W Li & A P Xiang

  2. Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China

    J Wang, J Cai, Y Huang, Q Ke, T Wang, Y Wang, W Li, C Lao & A P Xiang

  3. Biotherapy Center, Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

    J Cai & A P Xiang

  4. Department of Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

    Q Ke

  5. Department of Cardiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

    B Wu

  6. Department of Gastrointestinal-Pancreatic Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

    S Wang & W Song

  7. Department of Population Genetics and Prevention, Fuwai Hospital of Peking Union Medical College, Beijing, China

    X Han

  8. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

    W Li & A P Xiang

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  1. J Wang
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Correspondence to A P Xiang.

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Wang, J., Cai, J., Huang, Y. et al. Nestin regulates proliferation and invasion of gastrointestinal stromal tumor cells by altering mitochondrial dynamics. Oncogene 35, 3139–3150 (2016). https://doi.org/10.1038/onc.2015.370

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