Knockdown of metallopanstimulin-1 inhibits NF-κB signaling at different levels: the role of apoptosis induction of gastric cancer cells

Int J Cancer. 2012 Jun 15;130(12):2761-70. doi: 10.1002/ijc.26331. Epub 2011 Nov 29.


The ribosomal protein S27 (metallopanstimulin-1, MPS-1) has been reported to be a multifunctional protein, with increased expression in a number of cancers. We reported previously that MPS-1 was highly expressed in human gastric cancer. Knockdown of MPS-1 led to spontaneous apoptosis and repressed proliferation of human gastric cancer cells in vitro and in vivo. However, how does MPS-1 regulate these processes is unclear. Here we performed microarray and pathway analyses to investigate possible pathways involved in MPS-1 knockdown-induced apoptosis in gastric cancer cells. Our results showed that knockdown of MPS-1 inhibited NF-κB activity by reducing phosphorylation of p65 at Ser536 and IκBα at Ser32, inhibiting NF-κB nuclear translocation, and down-regulating its DNA binding activity. Furthermore, data-mining the Gene-Regulatory-Network revealed that growth arrest DNA damage inducible gene 45β (Gadd45β), a direct NF-κB target gene, played a critical role in MPS-1 knockdown-induced apoptosis. Over-expression of Gadd45β inhibited MPS-1 knockdown-induced apoptosis via inhibition of JNK phosphorylation. Taken together, these data revealed a novel pathway, the MPS-1/NF-κB/Gadd45β signal pathway, played an important role in MPS-1 knockdown-induced apoptosis of gastric cancer cells. This study sheds new light on the role of MPS-1/NF-κB in apoptosis and the possible use of MPS-1 targeting strategy in the treatment of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / metabolism*
  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Etoposide / pharmacology
  • HEK293 Cells
  • Humans
  • I-kappa B Kinase / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System
  • Membrane Potential, Mitochondrial
  • Metalloproteins / genetics
  • Metalloproteins / metabolism*
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • RNA Interference
  • RNA, Small Interfering
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Transcription Factor RelA / metabolism


  • Antigens, Differentiation
  • GADD45B protein, human
  • Metalloproteins
  • NF-kappa B
  • Nuclear Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • RPS27 protein, human
  • Ribosomal Proteins
  • Transcription Factor RelA
  • Etoposide
  • I-kappa B Kinase
  • JNK Mitogen-Activated Protein Kinases

Associated data

  • GEO/GSE28877