Annals of Surgical Oncology

, Volume 24, Issue 12, pp 3771–3779 | Cite as

FBXO50 Enhances the Malignant Behavior of Gastric Cancer Cells

  • Takashi Miwa
  • Mitsuro Kanda
  • Haruyoshi Tanaka
  • Chie Tanaka
  • Daisuke Kobayashi
  • Shinichi Umeda
  • Naoki Iwata
  • Masamichi Hayashi
  • Suguru Yamada
  • Tsutomu Fujii
  • Michitaka Fujiwara
  • Yasuhiro Kodera
Translational Research and Biomarkers

Abstract

Background

Challenges to our understanding the molecular mechanisms of the progression of gastric cancer (GC) must be overcome to facilitate the identification of novel biomarkers and therapeutic targets. In this article, we analyzed the expression of the gene encoding F-box-only 50 (FBXO50) and determined whether it contributes to the malignant phenotype of GC.

Methods

FBXO50 messenger RNA (mRNA) levels and copy numbers of the FBXO50 locus were determined in 10 GC cell lines and a nontumorigenic epithelial cell line. Polymerase chain reaction array analysis was performed to identify genes coordinately expressed with FBXO50. The effects of inhibiting FBXO50 on GC cell proliferation, adhesion, invasiveness, and migration were evaluated using a small interfering RNA targeted to FBXO50 mRNA. To evaluate the clinical significance of FBXO50 expression, we determined the levels of FBXO50 mRNA in tissues acquired from 200 patients with GC.

Results

The levels of FBXO50 mRNA were increased in five GC cell lines and positively correlated with those of ITGA5, ITGB1, MMP2, MSN, COL5A2, GNG11, and WNT5A. Copy number gain of the FBXO50 locus was detected in four GC cell lines. Inhibition of FBXO50 expression significantly decreased the proliferation, adhesion, migration, and invasiveness of GC cell lines. In clinical samples, high FBXO50 expression correlated with increased pT4, invasive growth, lymph node metastasis, and positive peritoneal lavage cytology. Patients with high FBXO50 expression had a significantly higher prevalence of recurrence after curative gastrectomy and were more likely to experience shorter overall survival.

Conclusions

FBXO50 may represent a biomarker for GC phenotypes and as a target for therapy.

Notes

Disclosure

None

Supplementary material

10434_2017_5882_MOESM1_ESM.doc (42 kb)
Supplementary material 1 (DOC 42 kb)
10434_2017_5882_MOESM2_ESM.tif (6.2 mb)
Supplementary material 2 (TIFF 6360 kb) FBXO50 mRNA expression levels in clinical tissues

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Copyright information

© Society of Surgical Oncology 2017

Authors and Affiliations

  • Takashi Miwa
    • 1
  • Mitsuro Kanda
    • 1
  • Haruyoshi Tanaka
    • 1
  • Chie Tanaka
    • 1
  • Daisuke Kobayashi
    • 1
  • Shinichi Umeda
    • 1
  • Naoki Iwata
    • 1
  • Masamichi Hayashi
    • 1
  • Suguru Yamada
    • 1
  • Tsutomu Fujii
    • 1
  • Michitaka Fujiwara
    • 1
  • Yasuhiro Kodera
    • 1
  1. 1.Department of Gastroenterological Surgery (Surgery II)Nagoya University Graduate School of MedicineNagoyaJapan

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