Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a critical driver in facilitating metastasis in breast cancer (BrCa). However, molecular mechanisms for the regulation of DAAM1 activation are only partially elucidated. In this research, the expression levels of YWHAZ and DAAM1 were examined by immunohistochemistry (IHC) staining in BrCa tissues. The functional roles of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)–DAAM1 axis and their regulator microRNA-613 (miR-613) in BrCa cells and associated molecular mechanisms were demonstrated in vitro. As results, the expression levels of DAAM1 and YWHAZ were significantly upregulated in BrCa tissues compared with normal tissues and remarkably associated with poor prognosis. Besides, DAAM1 and YWHAZ were positively correlated with each other in BrCa tissues. YWHAZ interacted and colocalized with DAAM1 in BrCa cells, which was essential for DAAM1-mediated microfilament remodeling and RhoA activation. Moreover, miR-613 directly targeted both YWHAZ and DAAM1, contributing to inhibiting BrCa cells migration via blocking the complex of YWHAZ–DAAM1. To sum up, these data reveal that YWHAZ regulates DAAM1 activation, and the YWHAZ–DAAM1 complex is directly targeted by the shared post-transcriptional regulator miR-613.

形态发生的蓬乱相关激活剂 1 (DAAM1) 是促进乳腺癌 (BrCa) 转移的关键驱动因素。然而，调节 DAAM1 激活的分子机制仅被部分阐明。在本研究中，通过免疫组织化学 (IHC) 染色在 BrCa 组织中检测 YWHAZ 和 DAAM1 的表达水平。酪氨酸 3-单加氧酶/色氨酸 5-单加氧酶激活蛋白 zeta (YWHAZ)-DAAM1 轴及其调节剂 microRNA-613 (miR-613) 在 BrCa 细胞中的功能作用和相关分子机制在体外得到证实。结果，与正常组织相比，BrCa 组织中 DAAM1 和 YWHAZ 的表达水平显着上调，并且与不良预后显着相关。除了，DAAM1 和 YWHAZ 在 BrCa 组织中相互呈正相关。YWHAZ 与 BrCa 细胞中的 DAAM1 相互作用并共定位，这对于 DAAM1 介导的微丝重塑和 RhoA 激活至关重要。此外，miR-613 直接靶向 YWHAZ 和 DAAM1，通过阻断 YWHAZ-DAAM1 复合物来抑制 BrCa 细胞迁移。总而言之，这些数据表明 YWHAZ 调节 DAAM1 的激活，并且 YWHAZ-DAAM1 复合物直接被共享的转录后调节剂 miR-613 靶向。