Exosome-transmitted p120-catenin suppresses hepatocellular carcinoma progression via STAT3 pathways

Mol Carcinog. 2019 Aug;58(8):1389-1399. doi: 10.1002/mc.23022. Epub 2019 Apr 17.

Abstract

Hepatocellular carcinoma (HCC) is a fatal disease with increasing morbidity and poor prognosis due to surgical recurrence and metastasis. Moreover, the molecular mechanism of HCC progression remains unclear. Although the role of p120-catenin (p120ctn) in liver cancer is well studied, the effects of secreted p120ctn transported by exosomes are less understood. Here, we show that p120ctn in exosomes secreted from liver cancer cells suppresses HCC cell proliferation and metastasis and expansion of liver cancer stem cells (CSCs). Mechanically, exosome p120ctn inhibits HCC cell progression via the STAT3 pathway, and the STAT3 inhibitor S3I-201 abolishes the observed effects on growth, metastasis, and self-renewal ability between exosome p120ctn-treated HCC cells and control cells. Taken together, we propose that p120ctn-containing exosomes derived from cancer cells inhibit the progression of liver cancer and may offer a new therapeutic strategy.

Keywords: STAT3; exosome; hepatocellular carcinoma; p120-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminosalicylic Acids / pharmacology
  • Benzenesulfonates / pharmacology
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Catenins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Delta Catenin
  • Exosomes / pathology
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Neoplasm Metastasis / pathology
  • Neoplastic Stem Cells / pathology*
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / metabolism*

Substances

  • Aminosalicylic Acids
  • Benzenesulfonates
  • Catenins
  • NSC 74859
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Delta Catenin
  • CTNND1 protein, human