E2F3 drives the epithelial-to-mesenchymal transition, cell invasion, and metastasis in breast cancer
E2F3 drives the epithelial-to-mesenchymal transition, cell invasion, and metastasis in breast cancer
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DOI：
10.1177/15353702211035693
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发表时间：
2021-08-09
影响因子：
3.2
通讯作者：
Saavedra, Harold, I
中科院分区：
文献类型：
--
作者：
Jusino, Shirley;Rivera-Rivera, Yainyrette;Saavedra, Harold, I
E2F3 是一种转录因子，如果过度表达，可能会引发肿瘤发生。此前，我们证明E2F3 mRNA在乳腺癌中过度表达，并且E2F3过度表达导致中心体扩增和不受调节的有丝分裂，这可以促进非整倍性和染色体不稳定，从而引发和维持肿瘤。此外，我们证明 E2F3 会导致有丝分裂调节因子 Shugoshin-1 的过度表达，而该调节因子直到最近在癌症中的作用尚不清楚。本研究旨在评估 E2F3 和 Shugoshin-1 在乳腺癌转移潜力中的作用。在这里，我们证明 E2F3 和 Shugoshin-1 沉默会导致两种间充质三阴性乳腺癌 (TNBC) 细胞系（MDA-MB-231 和 Hs578t）的细胞侵袭和迁移减少。此外，E2F3 和 Shugoshin-1 调节上皮间质转化相关基因的表达，例如 Snail、E-钙粘蛋白和多种基质金属蛋白酶。此外，E2F3 耗竭导致 NOD-scid Gamma 小鼠肿瘤生长和转移减少。这项研究的结果表明 E2F3 在转移进展中发挥关键作用，而 Shugoshin-1 则发挥新作用。这些结果可以通过干扰与 E2F3 和 Shugoshin-1 信号通路交叉的通路，进一步帮助改善 TNBC 靶向治疗。
E2F3 is a transcription factor that may initiate tumorigenesis if overexpressed. Previously, we demonstrated that E2F3 mRNA is overexpressed in breast cancer and that E2F3 overexpression results in centrosome amplification and unregulated mitosis, which can promote aneuploidy and chromosome instability to initiate and sustain tumors. Further, we demonstrated that E2F3 leads to overexpression of the mitotic regulator Shugoshin-1, which until recently had unknown roles in cancer. This study aims to evaluate the roles of E2F3 and Shugoshin-1 in breast cancer metastatic potential. Here we demonstrated that E2F3 and Shugoshin-1 silencing leads to reduced cell invasion and migration in two mesenchymal triple-negative breast cancer (TNBC) cell lines (MDA-MB-231 and Hs578t). Moreover, E2F3 and Shugoshin-1 modulate the expression of epithelial-to-mesenchymal transition-associated genes such as Snail, E-Cadherin, and multiple matrix metalloproteinases. Furthermore, E2F3 depletion leads to reductions in tumor growth and metastasis in NOD-scid Gamma mice. Results from this study suggest a key role for E2F3 and a novel role for Shugoshin-1 in metastatic progression. These results can further help in the improvement of TNBC targeted therapies by interfering with pathways that intersect with the E2F3 and Shugoshin-1 signaling pathways.