Advertisement

Tumor Biology

, Volume 36, Issue 2, pp 569–575 | Cite as

δ-Catenin promotes the malignant phenotype in breast cancer

Research Article
  • 248 Downloads

Abstract

δ-Catenin is a member of the p120 catenin family. Similar to p120ctn, δ-catenin contains nine central Armadillo repeats and binds to the juxtamembrane domain (JMD) of E-cadherin. We used immunohistochemistry to detect δ-catenin expression in breast carcinoma (128 cases), and δ-catenin mRNA and protein expression was detected by reverse transcription-polymerase chain reaction and Western blotting (45 cases). The effects of δ-catenin on the activity of small GTPases and the biological behavior of breast cancer cells were explored by pulldown, flow cytometry, methyl thiazolyl tetrazolium, and Matrigel invasion assays. The results showed that δ-catenin expression increased in breast cancer tissues and was associated with a higher degree of malignancy (invasive lobular breast cancer, high tumor-node-metastasis stage, lymph node metastasis, and C-erbB-2+) and poor prognosis. Postoperative survival was shorter in patients with δ-catenin-positive expression than in patients with negative expression. δ-Catenin may regulate Cdc42/Rac1 activity, promote proliferation and invasion of breast cancer cells, and alter cell cycle progression. We conclude that δ-catenin tends to overexpress in breast carcinoma and promotes the malignant phenotype.

Keywords

δ-Catenin p120ctn Small GTPase Cdc42 Rac1 

Notes

Acknowledgments

We sincerely thank Dr. Shun-ichi Nakamura at Kobe University, Japan, for kindly providing pCMV5-FLAG/δ-catenin. This work was supported by the National Natural Science Foundation of China (no. 81101779 to Di Zhang, MD; no. 30870977 and 81071905 to En-Hua Wang, MD; no. 81201844 to Jun-Yi Zhang, MD; no. 81372338 to Shu-Li Liu).

Conflicts of interest

None

References

  1. 1.
    Matter C, Pribadi M, Liu X, Trachtenberg JT. Delta-catenin is required for the maintenance of neural structure and function in mature cortex in vivo. Neuron. 2009;64(3):320–7.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    De Busk LM, Boelte K, Min Y, Lin PC. Heterozygous deficiency of delta-catenin impairs pathological angiogenesis. J Exp Med. 2010;207(1):77–84.CrossRefGoogle Scholar
  3. 3.
    Gu D, Tonthat NK, Lee M, Ji H, Bhat KP, Hollingsworth F, et al. Caspase-3 cleavage links delta-catenin to the novel nuclear protein ZIFCAT. J Biol Chem. 2011;286(26):23178–88.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Zhang H, Dai SD, Zhang D, Liu D, Zhang FY, Zheng TY, et al. Delta-catenin promotes the proliferation and invasion of colorectal cancer cells by binding to E-cadherin in a competitive manner with p120 catenin. Target Oncol. 2014;9(1):53–61.CrossRefPubMedGoogle Scholar
  5. 5.
    Brigidi GS, Sun Y, Beccano-Kelly D, Pitman K, Mobasser M, Borgland SL, et al. Palmitoylation of δ-catenin by DHHC5 mediates activity-induced synapse plasticity. Nat Neurosci. 2014;17(4):522–32.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kim H, He Y, Yang I, Zeng Y, Kim Y, Seo YW, et al. δ-Catenin promotes E-cadherin processing and activates β-catenin-mediated signaling: implications on human prostate cancer progression. Biochim Biophys Acta. 2012;1822(4):509–21.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Zhang JY, Wang Y, Zhang D, Yang ZQ, Dong XJ, Jiang GY, et al. delta-catenin promotes malignant phenotype of non-small cell lung cancer by non-competitive binding to E-cadherin with p120ctn in cytoplasm. J Pathol. 2010;222(1):76–88.PubMedGoogle Scholar
  8. 8.
    Lu Q, Lanford GW, Hong H, Chen YH. δ-Catenin as a potential cancer biomarker. Pathol Int. 2014;64(5):243–6.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Lu JP, Zhang J, Kim K, Case TC, Matusik RJ, Chen YH, et al. Human homolog of Drosophila Hairy and enhancer of split 1, Hes1, negatively regulates δ-catenin (CTNND2) expression in cooperation with E2F1 in prostate cancer. Mol Cancer. 2010;9:304.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Wang M, Dong Q, Zhang D, Wang Y. Expression of delta-catenin is associated with progression of human astrocytoma. BMC Cancer. 2011;11:514.CrossRefPubMedGoogle Scholar
  11. 11.
    Hatzfeld M. The p120 family of cell adhesion molecules. Eur J Cell Biol. 2005;84:205–14.CrossRefPubMedGoogle Scholar
  12. 12.
    Burger MJ, Tebay MA, Keith PA, Samaratunga HM, Clements J, Lavin MF, et al. Expression analysis of delta-catenin and prostate-specific membrane antigen: their potential as diagnostic markers for prostate cancer. Int J Cancer. 2002;100(2):228–37.CrossRefPubMedGoogle Scholar
  13. 13.
    Lu Q, Dobbs LJ, Gregory CW, Lanford GW, Revelo MP, Shappell S, et al. Increased expression of delta-catenin/neural plakophilin-related armadillo protein is associated with the down-regulation and redistribution of E-cadherin and p120ctn in human prostate cancer. Hum Pathol. 2005;36(10):1037–48.CrossRefPubMedGoogle Scholar
  14. 14.
    Arikkath J, Peng IF, Ng YG, Israely I, Liu X, Ullian EM, et al. Delta-catenin regulates spine and synapse morphogenesis and function in hippocampal neurons during development. J Neurosci. 2009;29(17):5435–42.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kawamura Y, Fan QW, Hayashi H, Michikawa M, Yanagisawa K, Komano H. Expression of the mRNA for two isoforms of neural plakophilin-related arm-repeat protein/delta-catenin in rodent neurons and glial cells. Neurosci Lett. 1999;277:185–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Lu Q, Paredes M, Medina M, et al. delta-catenin, an adhesive junction associated protein which promotes cell scattering. J Cell Biol. 1999;144:519–32.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Zhang JY, Zhang D, Wang EH. Overexpression of small GTPases directly correlates with expression of δ-catenin and their coexpression predicts a poor clinical outcome in nonsmall cell lung cancer. Mol Carcinog. 2013;52(5):338–47.CrossRefPubMedGoogle Scholar
  18. 18.
    Lane J, Martin T, Weeks HP, Jiang WG. Structure and role of WASP and WAVE in Rho GTPase signalling in cancer. Cancer Genomics Proteomics. 2014;11(3):155–65.PubMedGoogle Scholar
  19. 19.
    Zins K, Lucas T, Reichl P, Abraham D, Aharinejad S. A Rac1/Cdc42 GTPase-specific small molecule inhibitor suppresses growth of primary human prostate cancer xenografts and prolongs survival in mice. PLoS One. 2013;8(9):e74924. doi: 10.1371/journal.pone.0074924. eCollection 2013.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Dai SD, Wang Y, Zhang JY, Zhang D, Zhang PX, Jiang GY, et al. Upregulation of δ-catenin is associated with poor prognosis and enhances transcriptional activity through Kaiso in non-small-cell lung cancer. Cancer Sci. 2011;102(1):95–103.CrossRefPubMedGoogle Scholar
  21. 21.
    Nopparat J, Zhang J, Lu JP, Chen YH, Zheng D, Neufer PD, et al. δ-Catenin, a Wnt/β-catenin modulator, reveals inducible mutagenesis promoting cancer cell survival adaptation and metabolic reprogramming. Oncogene. 2014 Apr 14;0.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of PathologyThe First Affiliated Hospital and College of Basic Medical Sciences of China Medical UniversityShenyangChina
  2. 2.Department of PathologyThe Medical School and The Affiliated Hospital of Chifeng CollegeChifengChina

Personalised recommendations