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Activation of β-catenin signaling is critical for doxorubicin-induced epithelial–mesenchymal transition in BGC-823 gastric cancer cell line

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Tumor Biology

Abstract

The epithelial–mesenchymal transition (EMT) is a fundamental process governing morphogenesis in multicellular organisms and has recently been implicated in promoting carcinoma invasion and metastasis. Besides their therapeutic effects, accumulating evidences suggest that chemotherapeutic agents also induced EMT and enhanced the malignancy of treated cancer cells; however, the mechanism(s) still remains unclear. Here, we investigated the role of β-catenin signaling in doxorubicin (Dox)-induced EMT in human gastric cancer cell line BGC-823. We found that the transient treatment of Dox induced EMT and enhanced the in vitro migration ability of cancer cells. We also found that β-catenin signaling was activated upon Dox treatment. Inhibition of β-catenin by indomethacin (Indo) or siRNA suppressed Dox-induced EMT and decreased cancer cell migration ability. Our results showed that β-catenin signaling was critical to Dox-induced EMT. Indo and other β-catenin inhibitors may have a potential implication in prevention of gastric cancer metastasis.

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References

  1. Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science. 2011;331:1559–64.

    Article  PubMed  CAS  Google Scholar 

  2. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2007;100:57–70.

    Article  Google Scholar 

  3. Thiery JP. Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol. 2003;15:740–6.

    Article  PubMed  CAS  Google Scholar 

  4. Thiery JP, Acloque H, Huang RY, et al. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871–90.

    Article  PubMed  CAS  Google Scholar 

  5. Acloque H, Adams MS, Fishwick K, et al. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest. 2009;119:1438–49.

    Article  PubMed  CAS  Google Scholar 

  6. Pan JJ, Yang MH. The role of epithelial-mesenchymal transition in pancreatic cancer. J Gastrointest Oncol. 2011;2(3):151–6.

    PubMed  Google Scholar 

  7. Xiao D, He J. Epithelial mesenchymal transition and lung cancer. J Thorac Dis. 2010;2(3):154–9.

    PubMed  CAS  Google Scholar 

  8. Scheel C, Eaton EN, Li HJ. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell. 2011;145:926–40.

    Article  PubMed  CAS  Google Scholar 

  9. Kang Y, Massague J. Epithelial-mesenchymal transitions: Twist in development and metastasis. Cell. 2004;118:277–9.

    Article  PubMed  CAS  Google Scholar 

  10. Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. 2005;434:843–50.

    Article  PubMed  CAS  Google Scholar 

  11. Clevers H. Wnt/β-catenin signaling in development and disease. Cell. 2006;127:469–80.

    Article  PubMed  CAS  Google Scholar 

  12. Willert K, Jones KA. Wnt signaling: is the party in the nucleus? Genes Dev. 2006;20:1394–404.

    Article  PubMed  CAS  Google Scholar 

  13. Li J, Zhou BP. Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer. 2011;11:49–59.

    Article  PubMed  Google Scholar 

  14. Yang L, Lin C, Liu ZR. P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin. Cell. 2006;127:139–55.

    Article  PubMed  CAS  Google Scholar 

  15. Hanin L, Zaider M. Effects of surgery and chemotherapy on metastatic progression of prostate cancer: evidence from the natural history of the disease reconstructed through mathematical modeling. Cancers. 2011;3:3632–60.

    Article  Google Scholar 

  16. Li QQ, Xu JD, Wang WJ, et al. Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res. 2009;15:2657–65.

    Article  PubMed  CAS  Google Scholar 

  17. Bandyopadhyay A, Wang L, Agyin J, et al. Doxorubicin in combination with a small TGFbeta inhibitor: a potential novel therapy for metastatic breast cancer in mouse models. PLoS One. 2010;5:e10365.

    Article  PubMed  Google Scholar 

  18. Huang Q, Gumireddy K, Schrier M, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol. 2008;10:202–10.

    Article  PubMed  CAS  Google Scholar 

  19. Lu D, Cottam HB, Corr M, et al. Repression of β-catenin function in malignant cells by nonsteroidal anti-inflammatory drugs. PNAS. 2005;102:18567–71.

    Article  PubMed  CAS  Google Scholar 

  20. Hawcroft G, D'Amico M, Albanese C, et al. Indomethacin induces differential expression of β-catenin, γ-catenin and T-cell factor target genes in human colorectal cancer cells. Carcinogenesis. 2002;23:107–14.

    Article  PubMed  CAS  Google Scholar 

  21. Yamauchi K, Yang M, Hayashi K, et al. Induction of cancer metastasis by cyclophosphamide pretreatment of host mice: an opposite effect of chemotherapy. Cancer Res. 2008;68:516–20.

    Article  PubMed  CAS  Google Scholar 

  22. Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  24. Huls G, Koornstra JJ, Kleibeuker JH. Non-steroidal anti-inflammatory drugs and molecular carcinogenesis of colorectal carcinomas. Lancet. 2003;362:230–2.

    Article  PubMed  CAS  Google Scholar 

  25. Sandler RS, Halabi S, Baron JA, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med. 2003;348:883–90.

    Article  PubMed  CAS  Google Scholar 

  26. Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003;348:891–9.

    Article  PubMed  CAS  Google Scholar 

  27. Hawcroft G, Gardner SH, Hull MA. Activation of peroxisome proliferator-activated receptor does not explain the antiproliferative activity of the nonsteroidal anti-inflammatory drug indomethacin on human colorectal cancer cells. J Pharmacol Exp Ther. 2003;305:632–7.

    Article  PubMed  CAS  Google Scholar 

  28. Watanabe DX. Winning WNT: race to Wnt signaling inhibitors. PNAS. 2011;108:5929–30.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Rongfei Han and Jie Xiong equally contributed to this work. This study was supported by the National Natural Science Foundation of China (nos. 30971280, 30801336, and 81270607), Key Program of Natural Science Foundation of Hubei Province of China (no. 2011CDA044), and the Fundamental Research Fund for the Central Universities (no. 201130102020005).

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Correspondence to Qiuping Zhang.

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Han, R., Xiong, J., Xiao, R. et al. Activation of β-catenin signaling is critical for doxorubicin-induced epithelial–mesenchymal transition in BGC-823 gastric cancer cell line. Tumor Biol. 34, 277–284 (2013). https://doi.org/10.1007/s13277-012-0548-3

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  • DOI: https://doi.org/10.1007/s13277-012-0548-3

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