Morin impedes Yap nuclear translocation and fosters apoptosis through suppression of Wnt/β-catenin and NF-κB signaling in Mst1 overexpressed HepG2 cells

Exp Cell Res. 2017 Jun 15;355(2):124-141. doi: 10.1016/j.yexcr.2017.03.062. Epub 2017 Mar 31.


Recent clinical and experimental evidences strongly acclaim Yes-associated protein (Yap), a key oncogenic driver in liver carcinogenesis, as a therapeutic target. Of the known multiple schemes to inhibit Yap activity, activation of Mammalian Sterile 20-like Kinase 1 (Mst1), an upstream regulator of Yap, appears to be a promising one. In this study, we hypothesize that morin, a bioflavonoid, mediates its anti-cancer effect through the activation of Mst1/hippo signaling in liver cancer cells. To test this hypothesis, both full length Mst1 (F-Mst1) and kinase active N-terminal Mst1 (N-Mst1)-overexpressed HepG2 cells were used. Exposure of F-Mst1 overexpressed HepG2 cells to morin activated Mst1 by caspase-3 cleavage and thereby inhibited Yap nuclear translocation and fostered apoptosis. Morin suppressed NF-κB p65 and Wnt/β-catenin signaling through Mst1 activation via cleavage and phosphorylation, leading to cell death. Annexin-V/PI staining further confirmed the induction of apoptosis in morin treated F-Mst1 overexpressed cells. The present study shows that morin targets cell survival molecules such as NF-κB p65 and β-catenin through activation of hippo signaling. Therefore, morin could be considered as a potential anti-cancer agent against liver cancer.

Keywords: Apoptosis; Hippo signaling; Morin; Mst1; NF-κB signaling; β-catenin.

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis / drug effects*
  • Cell Nucleus / metabolism*
  • Dose-Response Relationship, Drug
  • Flavonoids / pharmacology*
  • Gene Expression Profiling
  • Hep G2 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B / metabolism*
  • Phosphoproteins / metabolism*
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Structure-Activity Relationship
  • Transcription Factors
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / drug effects*
  • YAP-Signaling Proteins
  • beta Catenin / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Flavonoids
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Phosphoproteins
  • Transcription Factors
  • Wnt Proteins
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • beta Catenin
  • morin
  • STK4 protein, human
  • Protein Serine-Threonine Kinases