Open Access

Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy

  • Authors:
    • Hongzhu Yan
    • Chengmin Qiu
    • Weiwei Sun
    • Minmin Gu
    • Feng Xiao
    • Jue Zou
    • Li Zhang
  • View Affiliations

  • Published online on: February 7, 2018     https://doi.org/10.3892/or.2018.6252
  • Pages: 1671-1681
  • Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer is the fifth most common cancer worldwide and Hippo-Yap is the novel signaling pathway which plays an important role in gastric cancer tumor development and progression. However, little insight is available to date regarding the specific role of Yes-associated protein (Yap) in gastric cancer. In the present study, we identified the mechanism through which Yap sustains gastric cancer viability and migration. Yap was greatly upregulated in gastric cancer cells and its expression promoted cellular migration and survival. Functional studies found that knockdown of Yap reduced the mitophagy activity, which subsequently caused mitochondrial apoptosis and cellular oxidative stress. The latter impaired adhesive protein expression, alleviated F-actin expression, blunted lamellipodium formation, leading to inhibition of cancer cell motility. Mechanistically, Yap preserved Sirtuin 1 (SIRT1) activity which manipulated mitofusin 2 (Mfn2) expression and subsequent mitophagy. Loss of Yap reduced SIRT1 expression and inhibited Mfn2-mediated mitophagy. Collectively, our results identified Hippo-Yap as a tumor promoter in gastric cancer that was mediated via activation of the SIRT1/Mfn2/mitophagy axis, with potential applications to gastric cancer therapy involving cancer survival and migration.
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April-2018
Volume 39 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yan H, Qiu C, Sun W, Gu M, Xiao F, Zou J and Zhang L: Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy. Oncol Rep 39: 1671-1681, 2018
APA
Yan, H., Qiu, C., Sun, W., Gu, M., Xiao, F., Zou, J., & Zhang, L. (2018). Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy. Oncology Reports, 39, 1671-1681. https://doi.org/10.3892/or.2018.6252
MLA
Yan, H., Qiu, C., Sun, W., Gu, M., Xiao, F., Zou, J., Zhang, L."Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy". Oncology Reports 39.4 (2018): 1671-1681.
Chicago
Yan, H., Qiu, C., Sun, W., Gu, M., Xiao, F., Zou, J., Zhang, L."Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy". Oncology Reports 39, no. 4 (2018): 1671-1681. https://doi.org/10.3892/or.2018.6252