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- Title
Knockdown of metallopanstimulin-1 inhibits NF-κB signaling at different levels: The role of apoptosis induction of gastric cancer cells.
- Authors
Yang, Zhong-Yin; Qu, Ying; Zhang, Qing; Wei, Min; Liu, Chuan-Xu; Chen, Xue-Hua; Yan, Min; Zhu, Zheng-Gang; Liu, Bing-Ya; Chen, Guo-Qiang; Wu, Ying-Li; Gu, Qin-Long
- 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.
- Publication
International Journal of Cancer, 2012, Vol 130, Issue 12, p2761
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.26331