Huaier polysaccharides suppress triple-negative breast cancer metastasis and epithelial-mesenchymal transition by inducing autophagic degradation of Snail

Cell & Bioscience

Yuzhao Yan¹  Minghao Wang¹  Zhaoyu Wang¹  Wei Liu¹  Ziwei Wu¹  Linxi Zhou¹  Zhen Zeng¹  Ying Hu¹  Qinwen Pan¹  Lingjuan Zeng¹  Jin Wu¹  Jun Jiang¹  Peng Tang¹  Yuan Tian² 

[1] Breast Disease Center, Southwest Hospital, Army Medical University, 30# Gaotanyan street, 400038, Chongqing, China;Breast Disease Center, Southwest Hospital, Army Medical University, 30# Gaotanyan street, 400038, Chongqing, China;Department of General Surgery, Linyi People’s Hospital, 276000, Linyi, China;

关键词: Triple-negative breast cancer;    Metastasis;    Invasion;    Huaier;    In vitro;    In vivo;   

DOI  :  10.1186/s13578-021-00682-6

来源: Springer

【 摘 要 】

BackgroundTriple-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.ResultsThis 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.ConclusionsThis 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.

【 授权许可】

CC BY