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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. \\nMethods 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. \\nResults 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. \\nConclusions FBXO50 may represent a biomarker for GC phenotypes and as a target for therapy. \\nElectronic supplementary material The online version of this article (doi: 10.1245/s10434-017-5882-7) contains supplementary material, which is available to authorized users.Despite its declining incidence, gastric cancer (GC) is the fifth most frequent cancer and the third leading cause of cancer-related death worldwide.1 Although therapeutic strategies have improved, the 5-year survival rates of patients with GC are \u003c30%.2,3 Metastasis and disease recurrence are two major obstacles to increasing long-term survival, and early intervention is required.4,5 A better understanding of the molecular mechanisms of GC progression is therefore required to identify biomarkers and therapeutic targets to improve diagnosis and treatment strategies. \\nF-box proteins contain at least one F-box domain that mediates protein–protein interactions and is associated with signal transduction and the regulation of the cell cycle.6, 7, 8 Little evidence is available that illuminates the role of genes that encode F-box only proteins (FBXO). 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  1. C100 医学部/医学系研究科
  2. C100a 雑誌掲載論文
  3. 学術雑誌

FBXO50 Enhances the Malignant Behavior of Gastric Cancer Cells

http://hdl.handle.net/2237/27332
http://hdl.handle.net/2237/27332
5f1c92a8-61f4-49aa-9217-21e5902b68ea
名前 / ファイル ライセンス アクション
kanda_manuscript.pdf kanda_manuscript.pdf ファイル公開日:2018/11/01 (871.7 kB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2018-01-31
タイトル
タイトル FBXO50 Enhances the Malignant Behavior of Gastric Cancer Cells
言語 en
著者 Miwa, Takashi

× Miwa, Takashi

WEKO 74917

en Miwa, Takashi

Search repository
Kanda, Mitsuro

× Kanda, Mitsuro

WEKO 74918

en Kanda, Mitsuro

Search repository
Tanaka, Haruyoshi

× Tanaka, Haruyoshi

WEKO 74919

en Tanaka, Haruyoshi

Search repository
Tanaka, Chie

× Tanaka, Chie

WEKO 74920

en Tanaka, Chie

Search repository
Kobayashi, Daisuke

× Kobayashi, Daisuke

WEKO 74921

en Kobayashi, Daisuke

Search repository
Umeda, Shinichi

× Umeda, Shinichi

WEKO 74922

en Umeda, Shinichi

Search repository
Iwata, Naoki

× Iwata, Naoki

WEKO 74923

en Iwata, Naoki

Search repository
Hayashi, Masamichi

× Hayashi, Masamichi

WEKO 74924

en Hayashi, Masamichi

Search repository
Yamada, Suguru

× Yamada, Suguru

WEKO 74925

en Yamada, Suguru

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Fujii, Tsutomu

× Fujii, Tsutomu

WEKO 74926

en Fujii, Tsutomu

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Fujiwara, Michitaka

× Fujiwara, Michitaka

WEKO 74927

en Fujiwara, Michitaka

Search repository
Kodera, Yasuhiro

× Kodera, Yasuhiro

WEKO 74928

en Kodera, Yasuhiro

Search repository
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
権利
言語 en
権利情報 The final publication is available at Springer via https://doi.org/10.1245/s10434-017-5882-7
キーワード
主題Scheme Other
主題 gastric cancer
キーワード
主題Scheme Other
主題 F-box-only 50
キーワード
主題Scheme Other
主題 progression
キーワード
主題Scheme Other
主題 biomarker
抄録
内容記述 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. \nMethods 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. \nResults 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. \nConclusions FBXO50 may represent a biomarker for GC phenotypes and as a target for therapy. \nElectronic supplementary material The online version of this article (doi: 10.1245/s10434-017-5882-7) contains supplementary material, which is available to authorized users.Despite its declining incidence, gastric cancer (GC) is the fifth most frequent cancer and the third leading cause of cancer-related death worldwide.1 Although therapeutic strategies have improved, the 5-year survival rates of patients with GC are <30%.2,3 Metastasis and disease recurrence are two major obstacles to increasing long-term survival, and early intervention is required.4,5 A better understanding of the molecular mechanisms of GC progression is therefore required to identify biomarkers and therapeutic targets to improve diagnosis and treatment strategies. \nF-box proteins contain at least one F-box domain that mediates protein–protein interactions and is associated with signal transduction and the regulation of the cell cycle.6, 7, 8 Little evidence is available that illuminates the role of genes that encode F-box only proteins (FBXO). For example, FBXO28 controls Myc-dependent transcription, is regulated during the cell cycle by cyclin-dependent kinase 1/2-mediated phosphorylation, and overexpression of FBXO28 is strongly associated with poor prognosis of patients with breast cancer.9 We identified F-box-only 50 (FBXO50; alternatively called non-specific cytotoxic cell receptor protein 1, NCCRP1) as a gene that is aberrantly expressed in metastatic GC by our previous transcriptome analysis.10,11 However, to our knowledge, no study reports the analysis of the expression and function of FBXO50 in GC.12 \nThese findings led us to hypothesize that FBXO50 is associated with the malignant phenotype of GC. Therefore, the present study was conducted to analyze the expression of FBXO50 in GC tissues and cell lines and to determine whether FBXO50 enhances the malignant phenotype of GC cells.
言語 en
内容記述タイプ Abstract
出版者
言語 en
出版者 Springer
言語
言語 eng
資源タイプ
資源タイプresource http://purl.org/coar/resource_type/c_6501
タイプ journal article
出版タイプ
出版タイプ AM
出版タイプResource http://purl.org/coar/version/c_ab4af688f83e57aa
DOI
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 https://doi.org/10.1245/s10434-017-5882-7
ISSN
収録物識別子タイプ PISSN
収録物識別子 1068-9265
書誌情報 en : Annals of Surgical Oncology

巻 24, 号 12, p. 3771-3779, 発行日 2017-11
著者版フラグ
値 author
URI
識別子 http://doi.org/10.1245/s10434-017-5882-7
識別子タイプ DOI
URI
識別子 http://hdl.handle.net/2237/27332
識別子タイプ HDL
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