致癌物2,3,7,8-四氯二苯并对二恶英对前列腺癌细胞中δ-连环蛋白稳定性及致瘤潜力的影响。
Effects of the carcinogen TCDD on δ-catenin stability and tumorigenic potential in prostate cancer cells.
作者信息
Niu Yue, Lee Hyoung Jae, Chen Zhiwei, Kim Hangun, Kim Kwonseop
机构信息
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University Gwangju 61186, Republic of Korea.
Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University Gwangju 61186, Republic of Korea.
出版信息
Am J Cancer Res. 2025 Apr 25;15(4):1939-1954. doi: 10.62347/WRBD9281. eCollection 2025.
δ-Catenin is a member of the p120-catenin subfamily of armadillo proteins and is known to be upregulated in prostate cancer, promoting tumorigenesis. Unfortunately, the molecular mechanism underlying this effect remains unclear. The carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been linked to an increased risk of prostate cancer. In this study, we explored the effect of TCDD on δ-catenin in prostate cancer cells. TCDD increased the protein levels of δ-catenin in a dose-dependent manner by enhancing its stability. Moreover, TCDD led to an increase in β-catenin expression but a decrease in E-cadherin levels. Further experiments revealed that TCDD stabilized the expression of δ-catenin by inhibiting its ubiquitination-mediated degradation. Finally, TCDD enhanced the motility and migration ability of prostate cancer cells through δ-catenin. These findings suggest that TCDD plays a role in stabilizing δ-catenin in prostate cancer cells, offering a new perspective on preventing δ-catenin degradation and potentially increasing the predictive value of δ-catenin for prostate cancer.
δ-连环蛋白是犰狳蛋白p120-连环蛋白亚家族的成员，已知在前列腺癌中上调，促进肿瘤发生。不幸的是，这种作用背后的分子机制仍不清楚。致癌物2,3,7,8-四氯二苯并对二恶英（TCDD）与前列腺癌风险增加有关。在本研究中，我们探讨了TCDD对前列腺癌细胞中δ-连环蛋白的影响。TCDD通过增强其稳定性以剂量依赖的方式增加了δ-连环蛋白的蛋白质水平。此外，TCDD导致β-连环蛋白表达增加，但E-钙黏蛋白水平降低。进一步的实验表明，TCDD通过抑制其泛素化介导的降解来稳定δ-连环蛋白的表达。最后，TCDD通过δ-连环蛋白增强了前列腺癌细胞的运动性和迁移能力。这些发现表明，TCDD在稳定前列腺癌细胞中的δ-连环蛋白方面发挥作用，为预防δ-连环蛋白降解以及潜在提高δ-连环蛋白对前列腺癌的预测价值提供了新的视角。
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