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Functional MUC4 suppress epithelial–mesenchymal transition in lung adenocarcinoma metastasis

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Tumor Biology

Abstract

The mucin MUC4 is a high molecular weight membrane-bound transmembrane glycoprotein that is frequently detected in invasive and metastatic cancer. The overexpression of MUC4 is associated with increased risks for several types of cancer. However, the functional role of MUC4 is poorly understood in lung adenocarcinoma. Using antisense-MUC4-RNA transfected adenocarcinoma cells, we discovered that the loss of MUC4 expression results in epithelial–mesenchymal transition (EMT). We found morphological alterations and the repression of the epithelial marker E-cadherin in transfected cells. Additionally, the loss of MUC4 caused the upregulation of the mesenchymal marker vimentin compared to control cells. Using a MUC4-knockdown versus control LTEP xenograft mice model (129/sv mice), we also found that EMT happened in lung tissues of MUC4-knockdown-LTEP xenograft mice. Moreover, antisense-MUC4-RNA transfected cells had a significantly increased cellular migration ability in vitro. The loss of MUC4 also occurred in lung adenocarcinoma patients with lymph node metastases. We further investigated MUC4 and found that it plays a critical role in regulating EMT by modulating β-catenin. Taken together, our study reveals a novel role for MUC4 in suppressing EMT and suggests that the assessment of MUC4 may function as a prognostic biomarker and could be a potential therapeutic target for lung adenocarcinoma metastasis.

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Acknowledgments

We thank Yang Wang (Tianjin Medical University of Cancer Institute and Hospital, Tianjin, China) for the assistance on the revision of the manuscript.

Conflicts of interest

None declared.

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Authors and Affiliations

  1. Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Liuwei Gao, Jun Liu, Bin Zhang, Hua Zhang, Daowei Wang, Tiemei Zhang, Yang Liu & Changli Wang

  2. National Clinical Research Centre of Cancer, Tianjin, China

    Liuwei Gao, Jun Liu, Bin Zhang, Hua Zhang, Daowei Wang, Tiemei Zhang, Yang Liu & Changli Wang

  3. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

    Liuwei Gao, Jun Liu, Bin Zhang, Hua Zhang, Daowei Wang, Tiemei Zhang, Yang Liu & Changli Wang

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  1. Liuwei Gao
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  2. Jun Liu
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  3. Bin Zhang
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  4. Hua Zhang
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  5. Daowei Wang
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  6. Tiemei Zhang
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  7. Yang Liu
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  8. Changli Wang
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Correspondence to Changli Wang.

Additional information

Liuwei Gao and Jun Liu contributed equally to this work.

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Gao, L., Liu, J., Zhang, B. et al. Functional MUC4 suppress epithelial–mesenchymal transition in lung adenocarcinoma metastasis. Tumor Biol. 35, 1335–1341 (2014). https://doi.org/10.1007/s13277-013-1178-0

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  • DOI: https://doi.org/10.1007/s13277-013-1178-0

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