Study on the abnormal centrosome regulation, leading to the chromosome instability in cancer

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590356
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SHINMURA Kazuya 浜松医科大学, 医学部, 准教授 (40321880)
• Project Period (FY): 2010 – 2012
• Keywords: 中心体 / 染色体不安定性 / がん / 中心体過剰複製 / PLK4 / SGOL1 / AID / 中心体サイクル / MUTYH

Research Abstract

t was revealed that PLK4 is overexpressed in a subset of gastric cancersand the overexpression of PLK4 induces centrosome amplification and chromosome instability. It was also revealed that PLK4 has activity to suppress primary cilia formation. A novel SGOL1 variant(SGOL1-P1), which is cancer-specific, was identified in colorectal cancer. Overexpression of the variant caused aberrant chromosome alignment, precociously separated chromatids, delayed mitotic progression, centrosome amplification, and chromosome instability. It was revealed that a part of AID is localized at the centrosomes, AID is aberrantly expressed in a subset of lung cancers, and the AID overexpression causesincreased spontaneous mutation.

Research Products

• [Journal Article] Role of base excision repair enzyme MUTYH in the repair of 8-hydroxyguanine and MUTYH-associated polyposis (MAP) (2012)
  • Author(s): Shinmura K, Goto M, Tao H, Sugimura H
  • Journal Title: Hereditary Genet Volume: 1 Pages: 111
  • Peer Reviewed
• [Journal Article] Impaired suppressive activities of human MUTYH variant proteins against oxidative mutagenesis (2012)
  • Author(s): Shinmura K, Goto M, Tao H, Matsuura S, Matsuda T, Sugimura H
  • Journal Title: World J Gastroenterol Volume: 18 Pages: 6935-6942
  • DOI: DOI:10.3748/wjg.v18.i47.6935
  • Peer Reviewed
• [Journal Article] Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization (2011)
  • Author(s): Kiyose S, Nagura K, Tao H, Igarashi H, Yamada H, Goto M, Maeda M, Kurabe N, Suzuki M, Tsuboi M, Kahyo T, Shinmura K, Hattori N, Sugimura H
  • Journal Title: Pathol Int Volume: 62 Pages: 477-484
  • DOI: DOI:10.1111/j.1440-1827.2012.02832.x
  • Peer Reviewed
• [Journal Article] Reduced expression of MUTYH with suppressive activity against mutations caused by 8-hydroxyguanine is a novel predictor of a poor prognosis in human gastric cancer (2011)
  • Author(s): Shinmura K, Goto M, Suzuki M, Tao H, Yamada H, Igarashi H, Matsuura S, Maeda M, Konno H, Matsuda T, Sugimura H
  • Journal Title: J Pathol Volume: 225 Pages: 414-423
  • DOI: DOI:10.1002/path.2953
  • Peer Reviewed
• [Journal Article] Suppression of hydroxyurea-induced centrosome amplification by NORE1A and down-regulation of NORE1A mRNA expression in non-small cell lung carcinoma (2011)
  • Author(s): Shinmura K, Tao H, Nagura K, Goto M, Matsuura S, Mochizuki T,SuzukiK, Tanahashi M, Niwa H, Ogawa H, Sugimura H
  • Journal Title: Lung Cancer Volume: 71 Pages: 19-27
  • DOI: DOI:10.1016/j.lungcan.2010.04.006
  • Peer Reviewed
• [Journal Article] A novel tumor-derived SGOL1 variant causes abnormal mitosis and unstable chromatid cohesion (2011)
  • Author(s): Kahyo T, Iwaizumi M, Shinmura K, Matsuura S, Nakamura T, Watanabe Y, Yamada H, Sugimura H
  • Journal Title: Oncogene Volume: 30 Pages: 4453-4463
  • DOI: DOI:10.1038/onc.2011.152
  • Peer Reviewed
• [Journal Article] Aberrant expression and mutation-inducing activity of AID in human lung cancer (2011)
  • Author(s): Shinmura K, Igarashi H, Goto M, Tao H, Yamada H, Matsuura S, Tajima M, Matsuda T, Yamane A, Funai K, Tanahashi M, Niwa H, Ogawa H, Sugimura H
  • Journal Title: Ann Surg Oncol Volume: 18 Pages: 2084-2092
  • DOI: DOI:10.1245/s10434-011-1568-8
  • Peer Reviewed
• [Journal Article] Adenine DNA glycosylase activity of 14 Human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer (2010)
  • Author(s): Goto M, Shinmura K, Nakabeppu Y, Tao H, Yamada H, Tsuneyoshi T, Sugimura H
  • Journal Title: Hum Mutat Volume: 31 Pages: E1861-1874
  • DOI: DOI:10.1002/humu.21363
  • Peer Reviewed
• [Journal Article] 大腸癌においてシュゴシン(hSgo1)の低下は染色体不安定性を誘導する (2010)
  • Author(s): 岩泉守哉、新村和也、山田英孝、伊熊睦博、椙村春彦
  • Journal Title: INTESTINE Volume: 14 Pages: 320-322
  • Peer Reviewed
• [Presentation] 酸化的損傷塩基の除去修復因子であるDNAグリコシラーゼの活性の個体差・異常とがん化に関する研究 (2012)
  • Author(s): 新村和也
  • Organizer: 第58回(平成24年度)日本病理学会秋期特別総会
  • Place of Presentation: 名古屋
  • Year and Date: 20121122-23
• [Presentation] 胃癌におけるMUTYHの8-hydroxyguanine誘発変異抑制活性とその発現レベルの予後予測に関する検討 (2012)
  • Author(s): 新村和也、後藤正憲、椙村春彦
  • Organizer: 第65回日本酸化ストレス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 20120607-08
• [Presentation] 胃癌におけるMUTYHの8-hydroxyguanine誘発変異抑制活性とその発現レベルの予後予測に関する検討 (2012)
  • Author(s): 新村和也、後藤正憲、鈴木雅也、陶弘、山田英孝、五十嵐久喜、松浦駿、前田松喜、今野弘之、松田知成、椙村春彦
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 20120426-28
• [Presentation] 非小細胞肺癌におけるSGOL1発現の臨床的意義 (2012)
  • Author(s): 松浦駿, 新村和也, 華表友暁, 乾直輝, 須田隆文, 椙村春彦, 千田金吾
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 20120420-22
• [Presentation] The activity and localization of 14 MUTYH variant proteins found in patients with colorectal polyposis and cancer (2011)
  • Author(s): Goto M, Shinmura K, Nakabeppu Y, Tao H, Yamada H, Tsuneyoshi T, Sugimura H
  • Organizer: 70th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
  • Year and Date: 20111003-05
• [Presentation] Aberrant expression and mutation-inducing activity of AID in human lung cancer (2011)
  • Author(s): Shinmura K, Igarashi H, Goto M, Tao H, Yamada H, Matsuura S, Matsuda T, Ogawa H, Sugimura H
  • Organizer: 70th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
  • Year and Date: 20111003-05
• [Presentation] 大腸ポリポーシスと大腸がんの患者で見つかった14種のMUTYH変異型タンパク質の活性と局在の評価 (2011)
  • Author(s): 後藤正憲、新村和也、中別府雄作、陶弘、山田英孝、常吉俊宏、椙村春彦
  • Organizer: がん予防大会2011(第18回日本がん予防学会、第34回日本がん疫学分子疫学研究会)
  • Place of Presentation: 京都
  • Year and Date: 20110620-21
• [Presentation] ヒト肺癌における脱アミノ化酵素AIDの異常発現と変異誘導能 (2011)
  • Author(s): 新村和也、五十嵐久喜、後藤正憲、陶弘、山田英孝、松浦駿、小川博、椙村春彦
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20110428-30
• [Presentation] Analysis of a novel shugoshin-like 1 variant from colon cancer (2010)
  • Author(s): Kahyo T, Iwaizumi M, Yamada H, Shinmura K, Sugimura H
  • Organizer: 69th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Osaka
  • Year and Date: 20100922-23
• [Presentation] Altered expression and the missensepolymorphism of the human base excision repair gene NTH1 in gastric cancer (2010)
  • Author(s): Goto M, Shinmura K, Konno H, Sugimura H
  • Organizer: 101th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: 101th Annual Meeting of the American Association for Cancer Research
  • Year and Date: 20100417-21
• [Book] Centrosome Abnormality and Human Lung Cancer in Lung Diseases - Selected State of the Art Reviews、Irusen EM (Ed.) (2012)
  • Author(s): Shinmura K, Sugimura H
  • Total Pages: 171-188
  • Publisher: InTech, Rijeka, Croatia