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Silencing survivin activates autophagy as an alternative survival pathway in HCC cells

  • Research Article
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Tumor Biology

Abstract

Autophagy is a survival mechanism that is activated in response to nutrient deprivation. The link between aberrant autophagy and cancer has been increasingly recognized. Survivin, an anti-apoptotic molecule, and the autophagy pathway are correlated with therapeutic responses to cancer. However, the role of autophagy in cancer progression remains unclear. Here, we generated survivin knockdown cells (survivin-KD) by introducing a short interfering RNA (siRNA) into hepatocellular carcinoma (HCC) cells, and we observed a 20 % reduction in the survival of these survivin-KD cells, as determined by MTT assay. In addition, an increased number of stress granules, increased positive staining by acridine orange and a shift in the high side scatter (SSC) cell population in flow cytometry analysis were observed in survivin-KD cells. Furthermore, electron microscopy revealed an increased number of autophagosomes in survivin-KD cells compared with scrambled control cells. Finally, we treated cells with an autophagy inhibitor, 3-MA, and observed a decrease in cell survival in survivin-KD cells compared with scrambled control cells. Our study suggests that an autophagy signal may be activated after the anti-apoptotic molecule survivin is suppressed. This finding implies that autophagy may be an alternative survival pathway in HCC cells and may provide a basis for the development of new therapeutic strategies for HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

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Acknowledgments

This study was supported by grants from Taipei Medical University and Shuang Ho Hospital (101TMU-SHH-9) and Ministry of Science and Technology (NSC-101-2314-B-038-016-MY3 and NSC-101-2314-B-038-029-MY3).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Yu-Jia Chang

  2. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Yu-Jia Chang, Chin-Sheng Hung & Po-Li Wei

  3. Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

    Yu-Jia Chang, Chin-Sheng Hung & Po-Li Wei

  4. Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

    Yu-Jia Chang, Chin-Sheng Hung & Po-Li Wei

  5. Taipei Medical University, Taipei, Taiwan

    Yu-Jia Chang, Chin-Sheng Hung & Po-Li Wei

  6. Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Linkou, Taiwan

    Li-Tzu Li

  7. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan

    Hsin-An Chen

  8. 250 Wu-Xing Street, 110, Taipei City, Taiwan

    Po-Li Wei

Authors
  1. Yu-Jia Chang
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  2. Li-Tzu Li
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  4. Chin-Sheng Hung
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  5. Po-Li Wei
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Corresponding author

Correspondence to Po-Li Wei.

Additional information

Yu-Jia Chang and Hsin-An Chen contributed equally to this study.

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Chang, YJ., Li, LT., Chen, HA. et al. Silencing survivin activates autophagy as an alternative survival pathway in HCC cells. Tumor Biol. 35, 9957–9966 (2014). https://doi.org/10.1007/s13277-014-2257-6

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  • DOI: https://doi.org/10.1007/s13277-014-2257-6

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