δ-Catenin promotes the malignant phenotype in breast cancer
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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.
Keywordsδ-Catenin p120ctn Small GTPase Cdc42 Rac1
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
- 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
- 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
- 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