The ubiquitin ligase RNF8 is known to induce epithelial‐to‐mesenchymal (EMT) transition and metastasis in triple‐negative breast cancer (TNBC). Besides EMT, Rho GTPases have been shown as key regulators in metastasis. In this study, we investigated the role of RNF8 in regulating Rho GTPases and cell motility. We find that RNF8 knockdown in TNBC cells attenuates the protein and mRNA levels of Ras homolog family member A (RHOA) and cell division cycle 42 (CDC42). We show that the formation of filopodia, focal adhesions, and the association of focal adhesions to stress fibers is impaired upon RNF8 knockdown. Cell migration is significantly inhibited by RNF8 knockdown. Our study suggests a potential novel role for RNF8 in mediating cell migration in TNBC through regulation of the Rho GTPases RHOA and CDC42.

中文翻译：

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泛素连接酶 RNF8 调节 Rho GTP 酶并促进三阴性乳腺癌细胞的细胞骨架变化和运动

已知泛素连接酶 RNF8 可诱导三阴性乳腺癌 (TNBC) 的上皮间质 (EMT) 转化和转移。除了 EMT，Rho GTPases 已被证明是转移的关键调节剂。在这项研究中，我们研究了 RNF8 在调节 Rho GTP 酶和细胞运动中的作用。我们发现 TNBC 细胞中的 RNF8 敲低减弱了 Ras 同源家族成员 A (RHOA) 和细胞分裂周期 42 (CDC42) 的蛋白质和 mRNA 水平。我们表明丝状伪足、粘着斑的形成以及粘着斑与应力纤维的关联在 RNF8 敲低后受损。RNF8 敲低显着抑制细胞迁移。我们的研究表明，RNF8 通过调节 Rho GTPases RHOA 和 CDC42 在介导 TNBC 细胞迁移中发挥潜在的新作用。