Abstract
BackgroundBreast 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.MethodsImmunohistochemistry (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.ResultsIn 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.ConclusionCollectively, 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.
Highlights
Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females
Ubiquitin protein ligase E3C (UBE3C) is overexpressed in BrCa To explore the effects of UBE3C on BrCa development, the expression of UBE3C was first assessed in 80 BrCa and matched breast tissue samples
We evaluated the expression levels of UBE3C in the nucleus and cytoplasm in BrCa tissues compared with breast tissues, and the results showed that most tumor samples exhibited higher UBE3C expression in the nucleus and cytoplasm (Fig. 1b, c)
Summary
Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. The mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized. Breast cancer (BrCa) has the highest morbidity among all cancers in females worldwide and may have caused more than 40,000 cancer-related deaths in the United States in 2019 [1]. BrCa in situ is usually not fatal to Ubiquitin protein ligase E3C (UBE3C), named HECTH2, is an important regulator of proteasome function that continuously cycles on and off proteasomes and stimulates associations by ubiquitin conjugates through cooperation with USP14 [7]. The role of UBE3C in BrCa and its potential mechanisms have not been well characterized
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