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

Authors
  • Tian, Yuan1, 2
  • Wu, Jin1
  • Zeng, Lingjuan1
  • Zhou, Linxi1
  • Hu, Ying1
  • Pan, Qinwen1
  • Liu, Wei1
  • Yan, Yuzhao1
  • Wu, Ziwei1
  • Wang, Zhaoyu1
  • Zeng, Zhen1
  • Tang, Peng1
  • Jiang, Jun1
  • Wang, Minghao1
  • 1 Army Medical University,
  • 2 Linyi People’s Hospital,
Type
Published Article
Journal
Cell & Bioscience
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Sep 04, 2021
Volume
11
Identifiers
DOI: 10.1186/s13578-021-00682-6
PMID: 34481526
PMCID: PMC8417980
Source
PubMed Central
Keywords
Disciplines
  • Research
License
Unknown

Abstract

Background 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. Results 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. Conclusions 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. Supplementary Information The online version contains supplementary material available at 10.1186/s13578-021-00682-6.

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