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Expression of Frat1 correlates with expression of β-catenin and is associated with a poor clinical outcome in human SCC and AC

  • Research Article
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Tumor Biology

Abstract

Overexpression of frequently rearranged in advanced T-cell lymphomas 1 (Frat1) has been reported in several human malignant tumors, but the relationship between Frat1 and β-catenin in lung cancer is still unclear. Our goal was to investigate the correlation between Frat1 and β-catenin in patients with lung cancers. Immunohistochemistry was performed in 110 cases of non-small cell lung cancer (NSCLC) with clinical follow-up. Results showed that both Frat1 and β-catenin were overexpressed in NSCLC. The expression of Frat1 and β-catenin was significantly correlated with tumor differentiation, TNM stage, and lymph node metastasis. Interestingly, the overexpression of β-catenin was positively correlated with the overexpression of Frat1 (correlation coefficient = 0.285; P = 0.003). In addition, overexpression of Frat1 and abnormal expression of β-catenin were found to represent a poor prognosis for the patients. Furthermore, based on the transfection of Frat1 and β-catenin, we found that Frat1 can upregulate the expression of β-catenin in BE1 cells.

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Abbreviations

Frat1:

Frequently rearranged in advanced T-cell lymphomas 1

NSCLC:

Non-small cell lung cancer

SCC:

Squamous cell carcinoma

Axin:

Axis inhibition protein

Frz:

Frizzled protein

Dvl:

Disheveled protein

References

  1. Bienz M, Clevers H. Linking colorectal cancer to Wnt signaling. Cell. 2000;103:311–20.

    Article  CAS  PubMed  Google Scholar 

  2. Lustig B, Behrens J. The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol. 2003;129:199–221.

    CAS  PubMed  Google Scholar 

  3. Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science. 2004;303:1483–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kimelman D, Xu W. Beta-catenin destruction complex: insights and questions from a structural perspective. Oncogene. 2006;25:7482–91.

    Article  CAS  PubMed  Google Scholar 

  5. Clements WM, Wang J, Sarnaik A, Kim OJ, MacDonald J, Fenoglio-Preiser C, Groden J, Lowy AM. Beta-catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. Cancer Res. 2002;62:3503–6.

    CAS  PubMed  Google Scholar 

  6. Hedgepeth CM, Deardorff MA, Rankin K, Klein PS. Regulation of glycogen synthase kinase 3beta and downstream Wnt signaling by axin. Mol Cell Biol. 1999;19:7147–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Thomas GM, Frame S, Goedert M, Nathke I, Polakis P, Cohen P. A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett. 1999;458:247–51.

    Article  CAS  PubMed  Google Scholar 

  8. Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH. Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex. EMBO J. 2003;22:494–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Haeseleer F, Pollet JF, Bollen A, Jacobs P. Molecular cloning and sequencing of the attachment site and integrase gene of the temperate mycobacteriophage FRAT1. Nucleic Acids Res. 1992;20:1420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang Y, Liu S, Zhu H, Zhang W, Zhang G, Zhou X, Zhou C, Quan L, Bai J, Xue L, Lu N, Xu N. Frat1 overexpression leads to aberrant activation of beta-catenin/TCF pathway in esophageal squamous cell carcinoma. Int J Cancer. 2008;123:561–8.

    Article  CAS  PubMed  Google Scholar 

  11. Wang Y, Hewitt SM, Liu S, Zhou X, Zhu H, Zhou C, Zhang G, Quan L, Bai J, Xu N. Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours. Br J Cancer. 2006;94:686–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Guo G, Mao X, Wang P, Liu B, Zhang X, Jiang X, Zhong C, Huo J, Jin J, Zhuo Y. The expression profile of FRAT1 in human gliomas. Brain Res. 2010;1320:152–8.

    Article  CAS  PubMed  Google Scholar 

  13. Guo G, Liu B, Zhong C, Zhang X, Mao X, Wang P, Jiang X, Huo J, Jin J, Liu X, Chen X. FRAT1 expression and its correlation with pathologic grade, proliferation, and apoptosis in human astrocytomas. Med Oncol. 2011;28:1–6.

    Article  PubMed  Google Scholar 

  14. Zhang Y, Yu JH, Lin XY, Miao Y, Han Y, Fan CF, Dong XJ, Dai SD, Wang EH. Overexpression of Frat1 correlates with malignant phenotype and advanced stage in human non-small cell lung cancer. Virchows Arch. 2011;459:255–63.

    Article  CAS  PubMed  Google Scholar 

  15. Jonkers J, Korswagen HC, Acton D, Breuer M, Berns A. Activation of a novel proto-oncogene, Frat1, contributes to progression of mouse T-cell lymphomas. EMBO J. 1997;16:441–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Freemantle SJ, Portland HB, Ewings K, Dmitrovsky F, DiPetrillo K, Spinella MJ, Dmitrovsky E. Characterization and tissue-specific expression of human GSK-3-binding proteins Frat1 and Frat2. Gene. 2002;291:17–27.

    Article  CAS  PubMed  Google Scholar 

  17. Kirikoshi H, Katoh M. Expression of WNT7A in human normal tissues and cancer, and regulation of WNT7A and WNT7B in human cancer. Int J Oncol. 2002;21:895–900.

    CAS  PubMed  Google Scholar 

  18. Lim SC, Lee MS. Significance of E-cadherin/beta-catenin complex and cyclin D1 in breast cancer. Oncol Rep. 2002;9:915–28.

    CAS  PubMed  Google Scholar 

  19. Hay E, Faucheu C, Suc-Royer I, Touitou R, Stiot V, Vayssiere B, Baron R, Roman-Roman S, Rawadi G. Interaction between LRP5 and Frat1 mediates the activation of the Wnt canonical pathway. J Biol Chem. 2005;280:13616–23.

    Article  CAS  PubMed  Google Scholar 

  20. Hino S, Michiue T, Asashima M, Kikuchi A. Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin. J Biol Chem. 2003;278:14066–73.

    Article  CAS  PubMed  Google Scholar 

  21. van Amerongen R, Nawijn MC, Lambooij JP, Proost N, Jonkers J, Berns A. Frat oncoproteins act at the crossroad of canonical and noncanonical Wnt-signaling pathways. Oncogene. 2010;29:93–104.

    Article  PubMed  Google Scholar 

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Acknowledgments

All lung tissue samples were obtained from the First Affiliated Hospital of China Medical University. The study was conducted according to the regulations of the institutional review boards at China Medical University (grants 30870977 and 81071905 to En-Hua Wang).

Conflicts of interest

The authors declare that they have no competing financial interests. No part of this article has been published or submitted elsewhere, and there are no financial or other relationships that might lead to a conflict of interest of this article. The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and each author believes that the manuscript represents honest work.

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Authors and Affiliations

  1. Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, People’s Republic of China

    Yong Zhang, Yang Han, Juan-Han Yu, Yuan Miao, Liang Wang & En-Hua Wang

  2. Institute of Pathology and Pathophysiology, China Medical University, Shenyang, 110001, People’s Republic of China

    Yong Zhang, Yang Han, Juan-Han Yu, Yuan Miao, Liang Wang & En-Hua Wang

  3. Department of Respiratory Internal Medicine, Shengjing Hospital, China Medical University, Shenyang, 110022, People’s Republic of China

    Rui Zheng

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  1. Yong Zhang
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  2. Yang Han
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  3. Rui Zheng
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  4. Juan-Han Yu
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  5. Yuan Miao
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  6. Liang Wang
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  7. En-Hua Wang
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Correspondence to En-Hua Wang.

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Zhang, Y., Han, Y., Zheng, R. et al. Expression of Frat1 correlates with expression of β-catenin and is associated with a poor clinical outcome in human SCC and AC. Tumor Biol. 33, 1437–1444 (2012). https://doi.org/10.1007/s13277-012-0394-3

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  • DOI: https://doi.org/10.1007/s13277-012-0394-3

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