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VGLL4 inhibits EMT in part through suppressing Wnt/β-catenin signaling pathway in gastric cancer

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Abstract

VGLL4 is a member of the Vestigial-like proteins that functions as a tumor suppressor, which directly competes with YAP for binding TEADs in several cancer types. Recently, an increasing number of studies have reported that VGLL4 acts as a crucial role in regulating cell mobility, migration, and invasion. However, little is known about the signaling mechanisms in regulating epithelial–mesenchymal transition (EMT) of gastric cancer. In our study, we confirmed that the expression level of VGLL4 was down-regulated in gastric cancer tissues, and reduced VGLL4 expression levels inhibited apoptosis and promoted proliferation, migration, and invasion. Additionally, we found a phenomenon that VGLL4 was associated with the change in nuclear location of β-catenin, which suggested that β-catenin was a significant downstream factor of VGLL4. These results suggest that VGLL4 suppressed EMT in part via negative regulation of Wnt/β-catenin signaling pathway. Taken together, our study demonstrated that VGLL4 is important in the process of suppressing tumor progression of gastric cancer and provided a potential therapeutic strategy for gastric cancer.

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References

  1. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  2. Wu Y, Zhou BP. New insights of epithelial–mesenchymal transition in cancer metastasis. Acta Biochim Biophys Sin. 2008;40:643–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Fuxe J, Vincent T, de Herreros AG. Transcriptional crosstalk between TGF-beta and stem cell pathways in tumor cell invasion: role of EMT promoting Smad complexes. Cell Cycle. 2010;9:2363–74.

    Article  CAS  PubMed  Google Scholar 

  4. Bates RC, Mercurio AM. The epithelial–mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther. 2005;4:365–70.

    Article  CAS  PubMed  Google Scholar 

  5. Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2:442–54.

    Article  CAS  PubMed  Google Scholar 

  6. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelialmesenchymal transitions in development and disease. Cell. 2009;139:871–90.

    Article  CAS  PubMed  Google Scholar 

  7. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7:131–42.

    Article  CAS  PubMed  Google Scholar 

  8. Yang J, Weinberg RA. Epithelial–mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14:818–29.

    Article  CAS  PubMed  Google Scholar 

  9. Chen J, Wang T, Zhou Y-C, et al. Aquaporin 3 promotes epithelial-mesenchymal transition in gastric cancer. J Exp Clin Cancer Res. 2014;33:38.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Shi Min, Zheng Dayong, Sun Li, et al. XB130 promotes proliferation and invasion of gastric cancer cells. J Transl Med. 2014;12:1.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9(4):265–73.

    Article  CAS  PubMed  Google Scholar 

  12. Bardeesy N, Cheng KH, Berger JH, Chu GC, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 2006;20(22):3130–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Wang Z, Li Y, Kong D, Banerjee S, et al. Acquisition of epithelial–mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Res. 2009;69(6):2400–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Fu Y, Zheng S, An N, et al. β-catenin as a potential key target for tumor suppression. Int J Cancer. 2011;129(7):1541–51.

    Article  CAS  PubMed  Google Scholar 

  15. Valenta T, Hausmann G, Basler K. The many faces and functions of β-catenin. EMBO J. 2012;31(12):2714–36.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Anson M, Crain-Denoyelle AM, Baud V, et al. Oncogenic β-catenin triggers an inflammatory response that determines the aggressiveness of hepatocellular carcinoma in mice. J Clin Invest. 2012;122(2):586–99.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Cadigan KM, Nusse R. Wnt signaling: a common theme in animal development. Genes Dev. 1997;11(24):3286–305.

    Article  CAS  PubMed  Google Scholar 

  18. Mao Y, Xu J, Li Z, et al. The role of nuclear β-catenin accumulation in the Twist2-induced ovarian cancer EMT. PLoS ONE. 2013;8(11):e78200.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Chen HH, Mullett SJ, Stewart AF. Vgl-4, a novel member of the vestigial-like family of transcription cofactors, regulates alpha1- adrenergic activation of gene expression in cardiac myocytes. J Biol Chem. 2004;279(29):30800–6.

    Article  CAS  PubMed  Google Scholar 

  20. Mielcarek M, Gunther S, Kruger M, et al. VITO-1, a novel vestigial related protein is predominantly expressed in the skeletal muscle lineage. Gene Expr Patterns. 2002;2(3–4):305–10.

    Article  CAS  PubMed  Google Scholar 

  21. Mielcarek M, Piotrowska I, Schneider A, et al. VITO-2, a new SID domain protein, is expressed in the myogenic lineage during early mouse embryonic development. Gene Expr Patterns. 2009;9(3):129–37.

    Article  CAS  PubMed  Google Scholar 

  22. Pobbati AV, Hong W. Emerging roles of TEAD transcription factors and its coactivators in cancers. Cancer Biol Ther. 2012;14(5):390–8.

    Article  Google Scholar 

  23. Pobbati AV, Chan SW, Lee I, et al. Structural and functional similarity between the Vgll1-TEAD and the YAP-TEAD complexes. Structure. 2012;20(7):1135–40.

    Article  CAS  PubMed  Google Scholar 

  24. Richardson AL, Wang ZC, De Nicolo A, et al. X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell. 2006;9(2):121–32.

    Article  CAS  PubMed  Google Scholar 

  25. Helias-Rodzewicz Z, Perot G, Chibon F, et al. YAP1 and VGLL3, encoding two cofactors of TEAD transcription factors, are amplified and overexpressed in a subset of soft tissue sarcomas. Genes Chromosom Cancer. 2012;49(12):1161–71.

    Article  Google Scholar 

  26. Mann KM, Ward JM, Yew CC, et al. Sleeping beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma. Proc Natl Acad Sci USA. 2012;109(16):5934–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Jin HS, Park HS, Shin JH, et al. A novel inhibitor of apoptosis protein (IAP)-interacting protein, Vestigial-like (Vgl)-4, counteracts apoptosis-inhibitory function of IAPs by nuclear sequestration. Biochem Biophys Res Commun. 2012;412(3):454–9.

    Article  Google Scholar 

  28. Jiao S, Wang H, Shi Z, et al. A peptide mimicking VGLL4 function acts as a YAP antagonist therapy against gastric cancer. Cancer Cell. 2014;25(2):166–80.

    Article  CAS  PubMed  Google Scholar 

  29. Xu MZ, Yao TJ, Lee NP, et al. Yes-associated protein is an independent prognostic marker in Hepatocellular carcinoma. Cancer. 2009;115:4576–85.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Xu W, Wang Z, Zhang W et al. Mutated K-ras activates CDK8 to stimulate the epithelial-to-mesenchymal transition in pancreatic cancer in part via the Wnt/β-catenin signaling pathway. Cancer Lett. 2015;356(2 Pt B):613–27.

    Article  CAS  PubMed  Google Scholar 

  31. Zha L, Zhang J, Tang W, et al. HMGA2 elicits EMT by activating the Wnt/b-catenin pathway in gastric cancer. Dig Dis Sci. 2013;58:724–33.

    Article  CAS  PubMed  Google Scholar 

  32. Zhang W, Gao Y, Li P, et al. VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex. Cell Res. 2014;24(3):331–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 81272753).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Hui Li, Ziwei Wang, Wei Zhang, Kun Qian, Gang Liao, Wei Xu & Shouru Zhang

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  1. Hui Li
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  2. Ziwei Wang
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  3. Wei Zhang
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  4. Kun Qian
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  5. Gang Liao
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  6. Wei Xu
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Correspondence to Ziwei Wang.

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Li, H., Wang, Z., Zhang, W. et al. VGLL4 inhibits EMT in part through suppressing Wnt/β-catenin signaling pathway in gastric cancer. Med Oncol 32, 83 (2015). https://doi.org/10.1007/s12032-015-0539-5

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  • DOI: https://doi.org/10.1007/s12032-015-0539-5

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