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致癌性泛素蛋白连接酶E3C(UBE3C)通过激活Wnt/β-连环蛋白信号通路促进乳腺癌进展。

Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling.

作者信息

Hang Chen, Zhao Shanojie, Wang Tiejun, Zhang Yan

机构信息

Department of Oncology, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, China.

Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, No. 48, Huaishu Road, Wuxi, 214023, China.

出版信息

Cancer Cell Int. 2021 Jan 6;21(1):25. doi: 10.1186/s12935-020-01733-7.

DOI:10.1186/s12935-020-01733-7
PMID:33407510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7789303/
Abstract

BACKGROUND

Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized.

METHODS

Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa.

RESULTS

In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells.

CONCLUSION

Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

摘要

背景

乳腺癌是全球最常见的女性恶性肿瘤,在女性所有癌症中发病率最高。不幸的是,导致乳腺癌患者预后不良的乳腺癌生长和转移机制尚未得到充分阐明。

方法

对包含80个样本的乳腺癌组织微阵列(TMA)进行免疫组织化学(IHC)检测,以评估泛素蛋白连接酶E3C(UBE3C)的表达。此外,进行了一系列细胞实验以揭示UBE3C在乳腺癌中的作用。

结果

在本研究中,我们首次确定UBE3C是乳腺癌生长和转移中的致癌因子。与相邻乳腺组织相比,乳腺癌组织中UBE3C表达上调。肿瘤细胞核UBE3C高表达的乳腺癌患者的总生存期(OS)明显低于核表达低的患者。在MCF-7和MDA-MB-453乳腺癌细胞中敲低UBE3C表达可抑制细胞体外增殖、迁移和侵袭,而在这些细胞中过表达UBE3C则产生相反的效果。此外,UBE3C促进β-连环蛋白核内积累,导致乳腺癌细胞中Wnt/β-连环蛋白信号通路激活。

结论

总体而言,这些结果表明UBE3C在乳腺癌的发生和发展中起关键作用,并且UBE3C可能是乳腺癌预防和治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/99dd9225db55/12935_2020_1733_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/1223e14b0411/12935_2020_1733_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/4f6d16af41e3/12935_2020_1733_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/45810a3545a0/12935_2020_1733_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/9afba98e0575/12935_2020_1733_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/3c0e157c68fb/12935_2020_1733_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/fd375c7f746f/12935_2020_1733_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/99dd9225db55/12935_2020_1733_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/1223e14b0411/12935_2020_1733_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/4f6d16af41e3/12935_2020_1733_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/45810a3545a0/12935_2020_1733_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/9afba98e0575/12935_2020_1733_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/3c0e157c68fb/12935_2020_1733_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/fd375c7f746f/12935_2020_1733_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2e7/7789303/99dd9225db55/12935_2020_1733_Fig7_HTML.jpg

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