Significance of FBX8 in progression of gastric cancer

Exp Mol Pathol. 2015 Jun;98(3):360-6. doi: 10.1016/j.yexmp.2015.03.015. Epub 2015 Mar 20.

Abstract

F-box only protein 8 (FBX8), a novel component of F-box proteins, has recently been observed in several malignancies. However, its clinical implication in the progression of gastric cancer still remains unclear. The aim of this study was to explore the role of FBX8 in gastric cancer (GC) and analyze its correlation with tumor progression and prognosis. The expression of FBX8 in GC cell lines and matched pairs of fresh gastric cancer tissues were detected by real-time RT-PCR and Western blotting. Immunohistochemistry was used to analyze clinicopathological patterns of FBX8 in 136 cases of clinical paraffin-embedded GC tissues. A series of functional assays were conducted to evaluate the effect of FBX8 on proliferation and invasion in vitro and metastasis in vivo. FBX8 was markedly down-regulated in GC tissues compared to adjacent normal tissues. Patients with low FBX8 had shorter overall survival time and poor prognosis. Knocking down FBX8 obviously promoted proliferation and invasion in BGC823 cells, while over-expression of FBX8 in SGC7901 and AGS cells had the opposite effects. Moreover, FBX8 was sufficient to suppress metastasis in nude mice. Down-regulation of FBX8 significantly correlates with invasion, metastasis and poor survival time in GC patients. FBX8 may serve as a promising therapeutic target for inhibition of GC metastasis.

Keywords: FBX8; Gastric cancer; Invasion; Metastasis; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation
  • F-Box Proteins / genetics*
  • F-Box Proteins / metabolism
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prognosis
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • F-Box Proteins
  • FBXO8 protein, human