title: Knockdown of metallopanstimulin-1 inhibits NF-κB signaling at different levels: the role of apoptosis induction of gastric cancer cells.
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.
authors.affiliation: Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Chuan-Xu
authors.initials: CX
authors.lastname: Liu
authors.forename: Xue-Hua
authors.initials: XH
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Zhu
authors.forename: Bing-Ya
authors.initials: BY
authors.lastname: Liu
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Wu
authors.forename: Qin-Long
authors.initials: QL
authors.lastname: Gu
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005047:Etoposide / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D053078:Membrane Potential, Mitochondrial; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D005047:Etoposide; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D008667:Metalloproteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D051996:Transcription Factor RelA; C086470:GADD45B protein, human; D000097642:GADD45 Proteins; C083686:RPS27 protein, human