Skip to main content
Log in

Expression and Significance of Twist, E-Cadherin, and N-Cadherin in Gastrointestinal Stromal Tumors

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Twist, a basic helix-loop-helix transcription factor, has been reported to play a key role in the metastatic progression of several types of cancer.

Aims

To investigate the expression and clinical significance of Twist, E-cadherin, and N-cadherin in gastrointestinal stromal tumors (GISTs).

Methods

The expression of Twist, E-cadherin, and N-cadherin in GISTs was determined by immunohistochemistry, and their relationship with clinicopathological characteristics was analyzed.

Results

The positive rates of Twist, E-cadherin, and N-cadherin in GISTs were 66.7 % (52/78), 35.9 % (28/78), and 75.6 % (59/78), respectively. Twist was expressed significantly more in GISTs with distant metastasis or local invasion (p < 0.05). Although E-cadherin was expressed significantly less in cases of GISTs with distant metastasis (p < 0.05), expression of N-cadherin did not differ significantly according to clinical and pathological characteristics (p > 0.05). Expression of Twist was correlated positively with E-cadherin (rs = −0.253, p = 0.026) and negatively with N-cadherin (rs = 0.245, p = 0.030).

Conclusions

Twist was expressed significantly more and E-cadherin significantly less in GISTs with metastasis, and expression of both was closely related to metastasis of GISTs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33:459–465.

    Article  PubMed  Google Scholar 

  2. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–580.

    Article  PubMed  CAS  Google Scholar 

  3. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–710.

    Article  PubMed  CAS  Google Scholar 

  4. Mazur MT, Clark HB. Gastric stromal tumors: reappraisal of histogenesis. Am J Surg Pathol. 1983;7:507–519.

    Article  PubMed  CAS  Google Scholar 

  5. Ng EH, Pollock RE, Munsell MF, Atkinson EN, Romsdahl MM. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg. 1992;215:68–77.

    Article  PubMed  CAS  Google Scholar 

  6. Dematteo RP, Lewis JJ, Leung D, et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 2000;231:51–58.

    Article  PubMed  CAS  Google Scholar 

  7. Yang J, Mani SA, Donaher JL, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–939.

    Article  PubMed  CAS  Google Scholar 

  8. Thisse B, el Messal M, Perrin-Schmitt F. The twist gene: isolation of a Drosophila zygotic gene necessary for the establishment of dorsoventral pattern. Nucleic Acids Res. 1987;15:3439–3453.

    Article  PubMed  CAS  Google Scholar 

  9. Kwok WK, Ling MT, Lee TW, et al. Up-regulation of TWIST in prostate cancer and its implication as a therapeutic target. Cancer Res. 2005;65:5153–5162.

    Article  PubMed  CAS  Google Scholar 

  10. Niu RF, Zhang L, Xi GM, et al. Up-regulation of Twist induces angiogenesis and correlates with metastasis in hepatocellular carcinoma. J Exp Clin Cancer Res. 2007;26:385–394.

    PubMed  CAS  Google Scholar 

  11. Yuen HF, Chan YP, Wong MLY, et al. Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis. J Clin Pathol. 2007;60:510–514.

    Article  PubMed  CAS  Google Scholar 

  12. Maestro R, Dei Tos AP, Hamamori Y, et al. Twist is a potential oncogene that inhibits apoptosis. Genes Dev. 1999;13:2207–2217.

    Article  PubMed  CAS  Google Scholar 

  13. Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol. 2008;39:1411–1419.

    Article  PubMed  Google Scholar 

  14. Kyo S, Sakaguchi J, Ohno S, et al. High Twist expression is involved in infiltrative endometrial cancer and affects patient survival. Hum Pathol. 2006;37:431–438.

    Article  PubMed  CAS  Google Scholar 

  15. Nenutil R, Smardova J, Pavlova S, et al. Discriminating functional and non-functional p53 in human tumors by p53 and MDM2 immuno-histochemistry. J Pathol. 2005;207:251–259.

    Article  PubMed  CAS  Google Scholar 

  16. Guilford P, Hopkins J, Harraway J, et al. E-cadherin germline mutations in familial gastric cancer. Nature. 1998;392:402–405.

    Article  PubMed  CAS  Google Scholar 

  17. Entz-Werle N, Lavaux T, Metzger N, et al. Involvement of MET/TWIST/APC combination or the potential role of ossification factors in pediatric high-grade osteosarcoma oncogenesis. Neoplasia. 2007;9:678–688.

    Article  PubMed  CAS  Google Scholar 

  18. Maestro R, Dei Tos AP, Hamamori Y, et al. Twist is a potential oncogene that inhibits apoptosis. Genes Dev. 1999;13:2207–2217.

    Article  PubMed  CAS  Google Scholar 

  19. Guo Y, Xie J, Rubin E, et al. Frzb, a secreted Wnt antagonist, decreases growth and invasiveness of fibrosarcoma cells associated with inhibition of Met signaling. Cancer Res. 2008;68:3350–3360.

    Article  PubMed  CAS  Google Scholar 

  20. Cheng GZ, Chan J, Wang Q, et al. Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel. Cancer Res. 2007;67:1979–1987.

    Article  PubMed  CAS  Google Scholar 

  21. Tran NL, Adams DG, Vaillancourt RR, et al. Signal transduction from N-cadherin increases Bcl-2. Regulation of the phosphatidylinositol 3-kinase/Akt pathway by homophilic adhesion and actin cytoskeletal organization. J Biol Chem. 2002;277:32905–32914.

    Article  PubMed  CAS  Google Scholar 

  22. Pulyaeva H, Bueno J, Polette M, et al. MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells. Clin Exp Metastasis. 1997;15:111–120.

    Article  PubMed  CAS  Google Scholar 

  23. Castilla MA, Moreno-Bueno G, Romero-Perez L, et al. Micro-RNA signature of the epithelial-mesenchymal transition in endometrial carcinosarcoma. J Pathol. 2011;223:72–80.

    Article  PubMed  CAS  Google Scholar 

  24. Eckert MA, Yang J. Targeting invadopodia to block breast cancer metastasis. Oncotarget. 2011;2:562–568.

    PubMed  Google Scholar 

  25. Angst BD, Marcozzi C, Magee AI. The cadherin superfamily. J Cell Sci. 2001;114:625–626.

    PubMed  CAS  Google Scholar 

  26. Greenspon J, Li R, Xiao L, et al. Sphingosine-1-phosphate regulates the expression of adherens junction protein E-cadherin and enhances intestinal epithelial cell barrier function. Dig Dis Sci. 2011;56:1342–1353.

    Article  PubMed  CAS  Google Scholar 

  27. Yang J, Eddy JA, Pan Y, et al. Integrated proteomics and genomics analysis reveals a novel mesenchymal to epithelial reverting transition in leiomyosarcoma through regulation of slug. Mol Cell Proteomics. 2010;9:2405–2413.

    Article  PubMed  CAS  Google Scholar 

  28. House MG, Guo M, Efron DT, et al. Tumor suppressor gene hypermethylation as a predictor of gastric stromal tumor behavior. J Gastrointest Surg. 2003;7:1004–1014.

    Article  PubMed  Google Scholar 

  29. Vesuna F, van Diest P, Chen JH, et al. Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer. Biochem Biophys Res Commun. 2008;367:235–241.

    Article  PubMed  CAS  Google Scholar 

  30. Alexander NR, Tran NL, Rekapally H, et al. N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1. Cancer Res. 2006;66:3365–3369.

    Article  PubMed  CAS  Google Scholar 

  31. Derycke LD, Bracke ME. N-cadherin in the spotlight of cell–cell adhesion, differentiation, embryogenesis, invasion and signalling. Int J Dev Biol. 2004;48:463–476.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Guizhou Social Development Research Project, Grant Number: SY[2010]3117.

Conflict of interest

The authors declare no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guoqing Liao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ding, J., Zhang, Z., Pan, Y. et al. Expression and Significance of Twist, E-Cadherin, and N-Cadherin in Gastrointestinal Stromal Tumors. Dig Dis Sci 57, 2318–2324 (2012). https://doi.org/10.1007/s10620-012-2186-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-012-2186-4

Keywords

Navigation