Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the targeted therapies are lacking for this type of cancer. We previously demonstrated that Huaier effectively improve 5-year OS and DFS in stage III TNBC patients, and the polysaccharides of Huaier (PS-T) have been identified as the major components of Huaier. However, the mechanisms of anti-tumor action of PS-T is unclear. This study aimed to investigate the effect of PS-T on TNBC cell invasion and migration. This study showed that PS-T inhibited cell invasion and migration both in vitro and in vivo by inducing autophagy to suppress epithelial-mesenchymal transition (EMT). Autophagy inhibitor LY294002 or knockdown of ATG5 suppressed the inhibitory effects of PS-T. In addition, as a key transcription factor controlling EMT initiation, Snail was found to be degraded by PS-T induced autophagy. In addition, overexpression of Snail reversed the inhibitory effects of PS-T. Furthermore, it was confirmed that the expression of Snail was inversely correlated with LC3 and associated with poor prognosis using immunohistochemistry and TCGA database analysis, respectively. This study demonstrated that PS-T could inhibit EMT in breast cancer cells by inducing autophagy to degrade Snail protein, thus improving the prognosis of TNBC, offering potential treatment alternatives for TNBC patients.

中文翻译：

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槐耳多糖通过诱导Snail自噬降解抑制三阴性乳腺癌转移和上皮间质转化

三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型，目前缺乏针对此类癌症的靶向治疗。我们之前已经证明槐耳可有效改善 III 期 TNBC 患者的 5 年 OS 和 DFS，并且槐耳多糖（PS-T）已被确定为槐耳的主要成分。然而，PS-T的抗肿瘤作用机制尚不清楚。本研究旨在探讨 PS-T 对 TNBC 细胞侵袭和迁移的影响。该研究表明，PS-T 通过诱导自噬来抑制上皮间质转化 (EMT)，从而在体外和体内抑制细胞侵袭和迁移。自噬抑制剂 LY294002 或 ATG5 的敲低抑制了 PS-T 的抑制作用。此外，作为控制 EMT 起始的关键转录因子，发现蜗牛被PS-T诱导的自噬降解。此外，Snail 的过表达逆转了 PS-T 的抑制作用。此外，分别使用免疫组织化学和 TCGA 数据库分析证实，Snail 的表达与 LC3 呈负相关，并与不良预后相关。该研究表明，PS-T 可以通过诱导自噬降解 Snail 蛋白来抑制乳腺癌细胞的 EMT，从而改善 TNBC 的预后，为 TNBC 患者提供潜在的治疗选择。分别。该研究表明，PS-T 可以通过诱导自噬降解 Snail 蛋白来抑制乳腺癌细胞的 EMT，从而改善 TNBC 的预后，为 TNBC 患者提供潜在的治疗选择。分别。该研究表明，PS-T可以通过诱导自噬降解Snail蛋白来抑制乳腺癌细胞的EMT，从而改善TNBC的预后，为TNBC患者提供潜在的治疗选择。