Elevated fibroblast growth factor-inducible 14 expression promotes gastric cancer growth via nuclear factor-κB and is associated with poor patient outcome

Oh Hyung Kwon, Sung Joon Park, Tae Wook Kang, Mirang Kim, Jeong Hwan Kim, Seung Moo Noh, Kyu Sang Song, Hyang Sook Yoo, Yuli Wang, David Pocalyko, Sang Gi Paik, Yeul Hong Kim, Seon Young Kim, Yong Sung Kim

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)73-81
Number of pages9
JournalCancer letters
Volume314
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1

Keywords

  • Anti-apoptosis
  • Cell growth
  • Fn14
  • Gastric cancer
  • NF-κB

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Kwon, O. H., Park, S. J., Kang, T. W., Kim, M., Kim, J. H., Noh, S. M., Song, K. S., Yoo, H. S., Wang, Y., Pocalyko, D., Paik, S. G., Kim, Y. H., Kim, S. Y., & Kim, Y. S. (2012). Elevated fibroblast growth factor-inducible 14 expression promotes gastric cancer growth via nuclear factor-κB and is associated with poor patient outcome. Cancer letters, 314(1), 73-81. https://doi.org/10.1016/j.canlet.2011.09.016