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LZTFL1 suppresses gastric cancer cell migration and invasion through regulating nuclear translocation of β-catenin

  • Original Article – Cancer Research
  • Published:
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Abstract

Purpose

Our previous work identified leucine zipper transcription factor-like 1 (LZTFL1) as a novel tumor suppressor gene, with its expression correlated with survival outcome in gastric cancer (GC) patients. This study focuses on the role of LZTFL1 in GC aggression and metastasis as well as its underlying molecular mechanisms.

Method

LZTFL1 immunohistochemical (IHC) staining on 311 paired normal/cancer tissue arrays were used to reconfirm the clinical significance of LZTFL1 expression. Transwell chamber assays were used to determine migration and invasive ability of GC cells. Gelatin zymography was employed to investigate the matrix metalloproteinases (MMPs) activity in tumor cells. Co-immunoprecipitation and Duolink in situ proximity ligation assay were used to analyze the interaction between LZTFL1 and β-catenin and the cellular localization of the interaction.

Result

IHC results indicated that patients with high LZTFL1 expression had a longer overall survival time (58 months, 95 % CI 28–128 months) than patients with low LZTFL1 expression (27 months, 95 % CI 23–35 months; p < 0.01). The expression level of LZTFL1 is associated with the degree of cell differentiation. LZTFL1 is necessary and sufficient to inhibit the expression of molecular markers associated with epithelial–mesenchymal transition (EMT) and cellular phenotypes associated with tumor cell EMT including the migration, invasion, and the expression and activities of MMPs of tumor cells. LZTFL1 binds β-catenin in the cytoplasm of the cell and inhibited its nuclear translocation.

Conclusion

LZTFL1 suppresses GC cell EMT by inhibiting β-catenin nuclear translocation. Re-expression of LZTFL1 in GC cells may be a potential therapeutic means to prevent GC metastasis.

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Acknowledgments

This study was supported by National Natural Science Foundation of China to Q.W. (Grant No. 81101581) and National Institute of Health (NIHRO1HL10947) and Cancer Prevention and Research Institute of Texas (CPRIT-RP120717) to Z.P.L.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Surgical Oncology and Institute of Clinical Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China

    Linbo Wang, Jufeng Guo, Qinchuan Wang, Jichun Zhou, Chenpu Xu, Rongyue Teng, Yongxia Chen & Qun Wei

  2. Department of International Medicine and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USA

    Qun Wei & Zhi-Ping Liu

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  1. Linbo Wang
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  2. Jufeng Guo
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Correspondence to Qun Wei or Zhi-Ping Liu.

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Linbo Wang and Jufeng Guo have contributed equally to this work.

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Wang, L., Guo, J., Wang, Q. et al. LZTFL1 suppresses gastric cancer cell migration and invasion through regulating nuclear translocation of β-catenin. J Cancer Res Clin Oncol 140, 1997–2008 (2014). https://doi.org/10.1007/s00432-014-1753-9

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