c-Myc, a key activator of cell proliferation and angiogenesis, promotes the development and progression of breast cancer. Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) is a multifunctional scaffold protein that suppresses the proliferation of breast cancer cells. In this study we investigated whether the cancer-suppressing effects of EBP50 resulted from its regulation of c-Myc signaling in human breast cancer MCF-7 cells in vitro and in vivo. We first found a significant correlation between EBP50 and c-Myc expression levels in breast cancer tissue, and demonstrated that EBP50 suppressed cell proliferation through decreasing the expression of c-Myc and its downstream proteins cyclin A, E and Cdc25A in MCF-7 cells. We further showed that EBP50 did not regulate c-Myc mRNA expression, but it promoted the degradation of c-Myc through the autophagic lysosomal pathway. Moreover, EBP50 promoted integration between c-Myc and p62, an autophagic cargo protein, triggering the autophagic lysosomal degradation of c-Myc. In EBP50-silenced MCF-7 cells, activation of autophagy by Beclin-1 promoted the degradation of c-Myc and inhibited cell proliferation. These results demonstrate that the EBP50/Beclin-1/p62/c-Myc signaling pathway plays a role in the proliferation in MCF-7 breast cancer cells: EBP50 stimulates the autophagic lysosomal degradation of c-Myc, thereby inhibits the proliferation of MCF-7 cells. Based on our results, promoting the lysosomal degradation of c-Myc might be a promising new strategy for treating breast cancer.

中文翻译：

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EBP50通过促进Beclin-1 / p62介导的c-Myc溶酶体降解来抑制MCF-7人乳腺癌细胞的增殖。

c-Myc是细胞增殖和血管生成的关键激活因子，可促进乳腺癌的发生和发展。Ezrin-radixin-moesin结合磷蛋白50（EBP50）是一种多功能支架蛋白，可抑制乳腺癌细胞的增殖。在这项研究中，我们调查了EBP50的抑癌作用是否是由于其在体外和体内对人乳腺癌MCF-7细胞中c-Myc信号的调控所致。我们首先发现乳腺癌组织中EBP50与c-Myc表达水平之间存在显着相关性，并证明EBP50通过降低MCF-7细胞中c-Myc及其下游蛋白cyclin A，E和Cdc25A的表达来抑制细胞增殖。我们进一步证明EBP50不能调节c-Myc mRNA的表达，但是它通过自噬溶酶体途径促进了c-Myc的降解。此外，EBP50促进了c-Myc与p62（一种自噬货物蛋白）之间的整合，从而触发了c-Myc的自噬溶酶体降解。在EBP50沉默的MCF-7细胞中，Beclin-1激活自噬促进了c-Myc的降解并抑制了细胞增殖。这些结果表明，EBP50 / Beclin-1 / p62 / c-Myc信号通路在MCF-7乳腺癌细胞的增殖中起作用：EBP50刺激c-Myc的自噬溶酶体降解，从而抑制MCF- 7个单元格。根据我们的结果，促进c-Myc的溶酶体降解可能是治疗乳腺癌的有希望的新策略。自噬货物蛋白，触发c-Myc自噬溶酶体降解。在EBP50沉默的MCF-7细胞中，Beclin-1激活自噬促进了c-Myc的降解并抑制了细胞增殖。这些结果表明，EBP50 / Beclin-1 / p62 / c-Myc信号通路在MCF-7乳腺癌细胞的增殖中起作用：EBP50刺激c-Myc的自噬溶酶体降解，从而抑制MCF- 7个单元格。根据我们的结果，促进c-Myc的溶酶体降解可能是治疗乳腺癌的有希望的新策略。自噬货物蛋白，触发c-Myc自噬溶酶体降解。在EBP50沉默的MCF-7细胞中，Beclin-1激活自噬促进了c-Myc的降解并抑制了细胞增殖。这些结果表明，EBP50 / Beclin-1 / p62 / c-Myc信号通路在MCF-7乳腺癌细胞的增殖中起作用：EBP50刺激c-Myc的自噬溶酶体降解，从而抑制MCF- 7个单元格。根据我们的结果，促进c-Myc的溶酶体降解可能是治疗乳腺癌的有希望的新策略。这些结果表明，EBP50 / Beclin-1 / p62 / c-Myc信号通路在MCF-7乳腺癌细胞的增殖中起作用：EBP50刺激c-Myc的自噬溶酶体降解，从而抑制MCF- 7个单元格。根据我们的结果，促进c-Myc的溶酶体降解可能是治疗乳腺癌的有希望的新策略。这些结果表明，EBP50 / Beclin-1 / p62 / c-Myc信号通路在MCF-7乳腺癌细胞的增殖中起作用：EBP50刺激c-Myc的自噬溶酶体降解，从而抑制MCF- 7个单元格。根据我们的结果，促进c-Myc的溶酶体降解可能是治疗乳腺癌的有希望的新策略。