title: Elevated fibroblast growth factor-inducible 14 expression promotes gastric cancer growth via nuclear factor-κB and is associated with poor patient outcome.
abstract: The fibroblast growth factor-inducible 14 (Fn14) gene encodes a type I transmembrane protein that belongs to the tumor necrosis factor receptor superfamily and regulates multiple cellular processes in diverse physiological and pathological conditions, including cancer. Here, we describe an important role for Fn14 in regulating the growth of gastric cancer cells. Previous gene expression data analysis demonstrated that Fn14 was up-regulated in various tumor tissues, including gastric cancer. Using qRT-PCR, we showed that Fn14 was overexpressed in gastric tumor tissues compared to normal tissues. Furthermore, Fn14 expression levels were inversely correlated with gastric cancer patient survival. Using ectopic overexpression and shRNA-mediated knockdown of Fn14, we demonstrated that the expression level of Fn14 affected cell growth in gastric cancer. The effect of Fn14 on cell growth was mediated by the NF-κB activity and eventually by the transcriptional regulation of the anti-apoptotic Bcl-2 family gene (Bcl-xL). These results suggest that Fn14 may play an important role in gastric tumor growth by regulating NF-κB-mediated anti-apoptosis and that Fn14 may be a useful prognostic marker for gastric cancer.
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
authors: Oh-Hyung
authors: OH
authors: Kwon
authors: Sung-Joon
authors: SJ
authors: Park
authors: Tae-Wook
authors: TW
authors: Kang
authors: Mirang
authors: M
authors: Kim
authors: Jeong-Hwan
authors: JH
authors: Kim
authors: Seung-Moo
authors: SM
authors: Noh
authors: Kyu-Sang
authors: KS
authors: Song
authors: Hyang-Sook
authors: HS
authors: Yoo
authors: Yuli
authors: Y
authors: Wang
authors: David
authors: D
authors: Pocalyko
authors: Sang-Gi
authors: SG
authors: Paik
authors: Yeul-Hong
authors: YH
authors: Kim
authors: Seon-Young
authors: SY
authors: Kim
authors: Yong Sung
authors: YS
authors: Kim
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000074049:Cytokine TWEAK; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000502:physiology*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013274:Stomach Neoplasms / Q000473:pathology*; D000074050:TWEAK Receptor; D016896:Treatment Outcome; D048069:Tumor Necrosis Factors / Q000502:physiology; D051020:bcl-X Protein / Q000032:analysis
chemical_list: C494811:BCL2L1 protein, human; D000074049:Cytokine TWEAK; D016328:NF-kappa B; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors; D051020:bcl-X Protein