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Silence of ezrin modifies migration and actin cytoskeleton rearrangements and enhances chemosensitivity of lung cancer cells in vitro

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Abstract

Ezrin, primarily acts as a linker between the plasma membrane and the cytoskeleton, is involved in many cellular functions, including regulation of actin cytoskeleton, control of cell shape, adhesion, motility, and modulation of signaling pathways. Although ezrin is now recognized as a key component in tumor metastasis, its roles and the underlying mechanisms remain unclear. In the present study, we chose highly metastatic human lung carcinoma 95D cells, which highly express the ezrin proteins, as a model to examine the functional roles of ezrin in tumor suppression. An ezrin-silenced 95D cell line was established using lentivirus-mediated short hairpin RNA method. CCK-8 assay and soft agar assay analysis showed that downregulation of ezrin significantly suppressed the tumorigenicity and proliferation of 95D cells in vitro. cell migration and invasion studies showed that ezrin-specific deficiency in the cells caused the substantial reduction of the cell migration and invasion. In parallel, it also induced rearrangements of the actin cytoskeleton. Flow cytometry assay showed that changes in the ezrin protein level significantly affected the cell cycle distribution and eventual apoptosis. Furthermore, further studies showed that ezrin regulated the expression level of E-cadherin and CD44, which are key molecules involved in cell growth, migration, and invasion. Meanwhile, the suppression of ezrin expression also sensitized cells to antitumor drugs. Altogether, our results demonstrated that ezrin played an important role in the tumorigenicity and metastasis of lung cancer cells, which will benefit the development of therapeutic strategy for lung cancer.

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Acknowledgments

This study was supported by the Medical and Health Science Research Foundation of Zhejiang Province, People’s Republic of China (2008A144) and the Nanjing military area commands ‘334’ High-level scientific and technological personnel training plan.

Conflict of interest

All the authors listed have seen the manuscript and approved to submit to your journal. We disclosed no conflicts of interest.

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Authors and Affiliations

  1. Department of Respiratory Disease, The 117th Hospital of PLA, 14 Lingyin Road, 310013, Hang Zhou, People’s Republic of China

    Qing-Yong Chen, De-Min Jiao, Li-Jun Wu, Jia Song & Jie Yan

  2. The Second Clinical College, Zhejiang Chinese Medical University, Hang Zhou, 310053, People’s Republic of China

    Wei Xu

  3. Department of Oncology Disease, The 117th Hospital of PLA, Hang Zhou, 310013, People’s Republic of China

    Jian-Guo Shi

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  1. Qing-Yong Chen
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  2. Wei Xu
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  3. De-Min Jiao
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  4. Li-Jun Wu
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  5. Jia Song
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  6. Jie Yan
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Correspondence to Qing-Yong Chen or Jian-Guo Shi.

Additional information

Wei Xu, De-Min Jiao contributed equally do this work.

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Chen, QY., Xu, W., Jiao, DM. et al. Silence of ezrin modifies migration and actin cytoskeleton rearrangements and enhances chemosensitivity of lung cancer cells in vitro. Mol Cell Biochem 377, 207–218 (2013). https://doi.org/10.1007/s11010-013-1586-x

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  • DOI: https://doi.org/10.1007/s11010-013-1586-x

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