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Knockdown of metallopanstimulin-1 inhibits NF-κB signaling at different levels: the role of apoptosis induction of gastric cancer cells.
- Source :
-
International journal of cancer [Int J Cancer] 2012 Jun 15; Vol. 130 (12), pp. 2761-70. Date of Electronic Publication: 2011 Nov 29. - Publication Year :
- 2012
-
Abstract
- 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.<br /> (Copyright © 2011 UICC.)
- Subjects :
- Antigens, Differentiation biosynthesis
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
NF-kappa B biosynthesis
NF-kappa B genetics
Nuclear Proteins genetics
Phosphorylation
RNA Interference
RNA, Small Interfering
RNA-Binding Proteins genetics
Ribosomal Proteins genetics
Stomach Neoplasms genetics
Transcription Factor RelA metabolism
Antigens, Differentiation metabolism
Apoptosis genetics
Metalloproteins metabolism
NF-kappa B metabolism
Nuclear Proteins metabolism
RNA-Binding Proteins metabolism
Ribosomal Proteins metabolism
Stomach Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 130
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 21796632
- Full Text :
- https://doi.org/10.1002/ijc.26331