YAP signaling in gastric cancer-derived mesenchymal stem cells is critical for its promoting role in cancer progression

Int J Oncol. 2017 Oct;51(4):1055-1066. doi: 10.3892/ijo.2017.4101. Epub 2017 Aug 23.

Abstract

Cancer-associated mesenchymal stem cells (MSCs) are critically involved in tumor development and progression. However, the mechanisms of action for MSCs in cancer remain largely unknown. Herein, we reported that the expression of Yes-associated protein 1 (YAP) was higher in gastric cancer derived mesenchymal stem cells (GC‑MSCs) than that in bone marrow derived MSCs (BM‑MSCs). YAP knockdown not only inhibited the growth, migration and invasion, and stemness of GC‑MSCs, but also suppressed their promoting effect on gastric cancer growth in vitro and in vivo. In addition, the interference of YAP expression in GC‑MSCs also attenuated the promoting role of gastric cancer cells in endothelial cell tube formation and migration. Mechanistically, YAP knockdown reduced the activation of β-catenin and its target genes in gastric cancer cells by GC‑MSCs. Taken together, these findings suggest that YAP activation in GC‑MSCs plays an important role in promoting gastric cancer progression, which may represent a potential target for gastric cancer therapy.

MeSH terms

  • Aged
  • Animals
  • Cell Cycle Proteins
  • Cell Proliferation / physiology
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Cell Cycle Proteins
  • Nuclear Proteins
  • Transcription Factors
  • YY1AP1 protein, human