It has been established that the acute phase protein, Serum amyloid A (SAA), which is usually synthesized by the liver, is also synthesized by cancer cells and cancer-associated cells in the tumor microenvironment. SAA also activates modulators of autophagy, such as the PI3K/Akt and MAPK signaling pathways. However, the role of SAA in autophagy in breast cancer still remains to be elucidated. The aim of this study was to investigate the role of SAA in the regulation of signaling pathways and autophagy in in vitro and in vivo models of breast cancer. The MDA-MB-231 and MCF7 cell lines were transiently transfected to overexpress SAA1. A tumor-bearing SAA1/2 knockout mouse model was also utilized in this study. SAA1 overexpression activated ERK signaling in the MDA-MB-231 cells, downregulated the PI3K pathway protein, PKB/Akt, in the MCF7 cell line, while SAA1/2 knockout also inhibited Akt. Furthermore, SAA1 overexpression in vitro downregulated autophagy, while the expression of SQSTM1/p62 was increased in the MCF7 cells, and SAA1/2 knockout induced autophagy in vivo. SAA overexpression in the MDA-MB-231 and MCF7 cells resulted in an increase in cell viability and increased the expression of the proliferation marker, MCM2, in the MCF7 cells. Furthermore, knockout of SAA1/2 resulted in an altered inflammatory profile, evident in the decrease of plasma IL-1β, IL-6 and IL-10, while increasing the plasma levels of MCP-1 and TNF-α. Lastly, SAA1/2 knockout promoted resistance to apoptosis and necrosis through the regulation of autophagy. SAA thus regulates autophagy in breast cancer cells to promote tumorigenesis.

已经确定，通常由肝脏合成的急性期蛋白血清淀粉样蛋白 A (SAA) 也由肿瘤微环境中的癌细胞和癌症相关细胞合成。SAA 还激活自噬调节剂，例如 PI3K/Akt 和 MAPK 信号通路。然而，SAA在乳腺癌自噬中的作用仍有待阐明。本研究的目的是探讨 SAA 在调控信号通路和自噬中的作用。体外和体内乳腺癌模型。瞬时转染 MDA-MB-231 和 MCF7 细胞系以过表达 SAA1。本研究还使用了带有肿瘤的 SAA1/2 敲除小鼠模型。SAA1 过表达激活 MDA-MB-231 细胞中的 ERK 信号传导，下调 MCF7 细胞系中的 PI3K 通路蛋白 PKB/Akt，而 SAA1/2 敲除也抑制 Akt。此外，SAA1 过表达体外自噬下调，而 MCF7 细胞中 SQSTM1/p62 的表达增加，SAA1/2 敲除诱导自噬体内. MDA-MB-231 和 MCF7 细胞中的 SAA 过表达导致细胞活力增加，并增加了 MCF7 细胞中增殖标志物 MCM2 的表达。此外，SAA1/2 的敲除导致炎症特征改变，明显降低血浆 IL-1β、IL-6 和 IL-10，同时增加血浆 MCP-1 和 TNF-α 水平。最后，SAA1/2 敲除通过调节自噬促进了对细胞凋亡和坏死的抵抗。因此，SAA 调节乳腺癌细胞中的自噬以促进肿瘤发生。