The Serum Amyloid A (SAA) family of proteins is associated with various pathological conditions, including cancer. However, their role in cancer is incompletely understood. Here, we investigated the role of SAA1 in cell cycle regulation, apoptosis, survival signaling, metabolism, and metastasis in models of triple-negative breast cancer (TNBC), using RNAi. Our data show that in untransformed epithelial cells (MCF12A), the knockdown of SAA1 induces the expression of cell cycle regulators (MCM2, p53), the activation of DNA repair (PARP synthesis), and survival signaling (NFκB). In contrast, knockdown of SAA1 in the TNBC cell line (MDA-MB-231) induced the expression p16 and shifted cells in the cell cycle from the S to G₂/M phase, without the activation of DNA repair. Moreover, in SAA1-deficient MDA-MB-231 and HCC70 cells, metabolism (NADH oxidation) continually increased while cell migration (% wound closure and the rate of wound closure) decreased. However, silencing of SAA1 altered epithelial and mesenchymal markers in MCF12A (E-cadherin, Laminin 1β, Vimentin) and MDA-MB-231 (α-Smooth muscle actin) cells, associated with the metastatic program of epithelial-mesenchymal transition. Nonetheless, our data provide evidence that SAA1 could potentially serve as a therapeutic target in TNBC.

血清淀粉样蛋白 A (SAA) 蛋白家族与各种病理状况有关，包括癌症。然而，它们在癌症中的作用尚不完全清楚。在这里，我们使用 RNAi 研究了 SAA1 在三阴性乳腺癌 (TNBC) 模型中的细胞周期调节、细胞凋亡、存活信号、代谢和转移中的作用。我们的数据显示，在未转化的上皮细胞 (MCF12A) 中，SAA1的敲低诱导细胞周期调节因子 (MCM2、p53) 的表达、DNA 修复的激活（PARP 合成）和存活信号 (NFκB)。相比之下，TNBC 细胞系 (MDA-MB-231)中SAA1 的敲低诱导了 p16 的表达，并将细胞周期中的细胞从 S 转移到 G ₂/M 期，未激活 DNA 修复。此外，在缺乏 SAA1 的 MDA-MB-231 和 HCC70 细胞中，代谢（NADH 氧化）持续增加，而细胞迁移（伤口闭合百分比和伤口闭合率）下降。然而，SAA1 的沉默改变了 MCF12A（E-钙粘蛋白、层粘连蛋白 1β、波形蛋白）和 MDA-MB-231（α-平滑肌肌动蛋白）细胞中的上皮和间充质标志物，这与上皮-间充质转化的转移程序有关。尽管如此，我们的数据提供证据表明 SAA1 可能作为 TNBC 的治疗靶点。