Alteration of polarity protein PAR-3 in esophageal squamous cell carcinoma

• Project/Area Number: 23590470
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: YASUI Kohichiroh 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (30323695)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: PAR-3 / PARD3 / 食道扁平上皮癌 / タイトジャンクション / 細胞極性 / 転移 / ZO-1 / 欠失 / 細胞接着

Research Abstract

We investigated DNA copy number aberrations in human esophageal squamous cell carcinoma (ESCC) cell lines using a high-density oligonucleotide microarray and found a homozygous deletion of PARD3 (the gene encoding PAR-3). The PAR-3 protein is implicated in the formation of tight junctions at epithelial cell-cell contacts. Exogenous expression of PARD3 in ESCC cells lacking this gene enhanced the recruitment of ZO-1, a marker of tight junctions, to sites of cell-cell contact. Conversely, knockdown of PARD3 in ESCC cells expressing this gene caused a disruption of ZO-1 localization at cell-cell borders. Expression of PARD3 was significantly reduced in primary ESCC tumors compared with their nontumorous counterparts, and this reduced expression was associated with positive lymph node metastasis and poor differentiation. Our results suggest that deletion and reduced expression of PARD3 may be a novel mechanism that drives the progression of ESCC.

Research Products

• [Journal Article] Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma. (2014)
  • Author(s): Dohi O, Yasui K, Gen Y, Takada H, Endo M, Tsuji K, Konishi C, Yamada N, Mitsuyoshi H, Naito Y, Tanaka S, Arii S, Yoshikawa T.
  • Journal Title: Int J Oncol, Volume: 42(2) Issue: 2 Pages: 411-418
  • DOI: 10.3892/ijo.2012.1724
  • Peer Reviewed
• [Journal Article] Aberrant expression of the PHF14 gene in biliary tract cancer cells. (2013)
  • Author(s): Akazawa T, Yasui K, Gen Y, Yamada N, Tomie A, Dohi O, Mitsuyoshi H, Yagi N, Itoh Y, Naito Y, Yoshikawa T.
  • Journal Title: Oncol Lett Volume: 5 Issue: 6 Pages: 1849-1853
  • DOI: 10.3892/ol.2013.1278
  • Peer Reviewed
• [Journal Article] SOX2 promotes tumor growth of esophageal squamous cell carcinoma via the AKT/ mTORC1 signaling pathway. (2013)
  • Author(s): Gen Y, Yasui K, Nishikawa T, Yoshikawa T.
  • Journal Title: Cancer Sci Volume: 104 Issue: 7 Pages: 810-816
  • DOI: 10.1111/cas.12155
  • Peer Reviewed
• [Journal Article] Selective accumulation of platinum and formation of platinum-DNA adducts in hepatocellular carcinoma after transarterial chemoembolization with miriplatin. (2013)
  • Author(s): Yasui K, Takashima H, Miyagawa M, Miyazawa K, Ochiai T, Mukaisho K, Amaike H, Ueda K, Morikawa J, Otsuji E, Yoshikawa T.
  • Journal Title: Hepatol Res Volume: 43 Issue: 10 Pages: 1093-1099
  • DOI: 10.1111/hepr.12059
  • Peer Reviewed
• [Journal Article] Rosuvastatin ameliorates high-fat and high-cholesterol diet-induced nonalcoholic steatohepatitis in rats (2013)
  • Author(s): Okada Y, Yamaguchi K, Nakajima T, Nishikawa T, Jo M, Mitsumoto Y, Kimura H, Nishimura T, Tochiki N, Yasui K, Mitsuyoshi H, Minami M, Kagawa K, Okanoue T, Itoh Y
  • Journal Title: Liver Int Volume: 33 Issue: 2 Pages: 301-311
  • DOI: 10.1111/liv.12033
  • Peer Reviewed
• [Journal Article] Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus (2013)
  • Author(s): Shima T, Uto H, Ueki K, Takamura T, Kohgo Y, Kawata S, Yasui K, Park H, Nakamura N, Nakatou T, Tanaka N, Umemura A, Mizuno M, Tanaka J, Okanoue T
  • Journal Title: J Gastroenterol Volume: 48 Issue: 4 Pages: 515-525
  • DOI: 10.1007/s00535-012-0653-5
  • Peer Reviewed
• [Journal Article] FGF3/FGF4 amplification and multiple lung metastases in responders to sorafenib in hepatocellular carcinoma. (2013)
  • Author(s): Arao T, Ueshima K, Matsumoto K, Nagai T, Kimura H, Hagiwara S, Sakurai T, Haji S, Kanazawa A, Hidaka H, Iso Y, Kubota K, Shimada M, Utsunomiya T, Hirooka M, Hiasa Y, Toyoki Y, Hakamada K, Yasui K, Kumada T, Toyoda H, Sato S, Hisai H, Kuzuya T, Tsuchiya K, Izumi N, Arii S, Nishio K, Kudo M.
  • Journal Title: Hepatology Volume: 57 Issue: 4 Pages: 1407-1415
  • DOI: 10.1002/hep.25956
  • Peer Reviewed
• [Journal Article] Prediction of a favorable clinical course in hepatitis C virus carriers with persistently normal serum alanine aminotransferase levels: A long-term follow-up study (2013)
  • Author(s): Nishimura T, Yamaguchi K, Fujii H, Okada Y, Yokomizo C, Niimi T, Sumida Y, Yasui K, Mitsuyoshi H, Minami M, Umemura A, Shima T, Okanoue T, Itoh Y.
  • Journal Title: Hepatol Res Volume: 43 Issue: 5 Pages: 557-562
  • DOI: 10.1111/j.1872-034x.2012.01091.x
  • Peer Reviewed
• [Journal Article] Alterations of the SWI/SNF chromatin remodeling subunit-BRG1 and BRM in hepatocellular carcinoma (2012)
  • Author(s): Endo M, Yasui K, Zen Y, Gen Y, Zen K, Tsuji , Dohi O, Mitsuyoshi H, Tanaka S, Taniwaki M, Nakanuma Y, Arii S, Yoshikawa T
  • Journal Title: Liver Int Volume: 33(1) Issue: 1 Pages: 105-172013
  • DOI: 10.1111/liv.12005
  • Peer Reviewed
• [Journal Article] Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese. (2012)
  • Author(s): Kawaguchi T
  • Journal Title: PLoS One Volume: 7 Issue: 6 Pages: e38322-e38322
  • DOI: 10.1371/journal.pone.0038322
  • Peer Reviewed
• [Journal Article] Clinical and pathological progression of non-alcoholic steatohepatitis to hepatocellular carcinoma (2012)
  • Author(s): Yasui K, Hashimoto E, Tokushige K, Koike K, Shima T, Kanbara Y, Saibara T, Uto H, Takami S, Kawanaka M, Komorizono Y, Okanoue T, and The Japan NASH Study Group.
  • Journal Title: Hepatol Res Volume: 42 Issue: 8 Pages: 767-773
  • DOI: 10.1111/j.1872-034x.2012.00986.x
  • Peer Reviewed
• [Journal Article] High expression of p300 in HCC predicts shortened overall survival in association with enhanced epithelial mesenchymal transition of HCC cells (2011)
  • Author(s): Yokomizo C, Yamaguchi K, Itoh Y, Nishimura T, Umemura A, Minami M, Yasui K, Mitsuyoshi H, Fujii H, Tochiki N, Nakajima T, Okanoue T, Yoshikawa T
  • Journal Title: Cancer Lett Volume: 310 Issue: 2 Pages: 140-147
  • DOI: 10.1016/j.canlet.2011.06.030
  • Peer Reviewed
• [Journal Article] Oxidative stress is closely associated with tumor angiogenesis of hepatocellular carcinoma (2011)
  • Author(s): Jo M, Nishikawa T, Nakajima T, Okada Y, Yamaguchi K, Mitsuyoshi H, Yasui K, Minami M, Iwai M, Kagawa K, Itoh Y, Yoshikawa T
  • Journal Title: J Gastroenterol Volume: 46 Issue: 6 Pages: 809-821
  • DOI: 10.1007/s00535-011-0392-z
  • Peer Reviewed
• [Journal Article] Japan NASH Study Group, Ministry of Health, Labour, and Welfare of Japan : Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma (2011)
  • Author(s): Yasui K, Hashimoto E, Komorizono Y, Saibara T
  • Journal Title: Clin Gastroenterol Hepatol Volume: 9 Issue: 5 Pages: 428-433
  • DOI: 10.1016/j.cgh.2011.01.023
  • Peer Reviewed
• [Journal Article] Nonalcoholic steatohepatitis and increased risk of chronic kidney disease (2011)
  • Author(s): Yasui K, Sumida Y, Mori Y, Mitsuyoshi H, Minami M, Itoh Y, Kanemasa K, Matsubara H, Okanoue T, Yoshikawa T
  • Journal Title: Metabolism Volume: 60 Issue: 5 Pages: 735-739
  • DOI: 10.1016/j.metabol.2010.07.022
• [Journal Article] Impact of amino acid substitutions in the hepatitis C virus genotype 1b core region on liver steatosis and glucose tolerance in non-cirrhotic patients without overt diabetes (2011)
  • Author(s): Sumida Y, Kanemasa K, Hara T, Inada Y, Sakai K, Imai S, Yoshida N, Yasui K, Itoh Y, Okanoue T, Yoshikawa T
  • Journal Title: J Gastroenterol Hepatol Volume: 26 Issue: 5 Pages: 836-842
  • DOI: 10.1111/j.1440-1746.2010.06568.x
  • Peer Reviewed
• [Journal Article] Japan Study Group of Nonalcoholic Fatty Liver Disease(JSG-NAFLD): A simple clinical scoring system using ferritin (2011)
  • Author(s): Sumida Y, Yoneda M, Saibara T, Okanoue T
  • Journal Title: fasting insulin, and type IV collagen 7S for predicting steatohepatitis in nonalcoholic fatty liver disease. J Gastroenterol Volume: 46 Issue: 2 Pages: 257-268
  • DOI: 10.1007/s00535-010-0305-6
  • Peer Reviewed
• [Journal Article] Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease (2011)
  • Author(s): Park H, Shima T, Yamaguchi K, Mitsuyoshi H, Minami M, Yasui K, Itoh Y, Yoshikawa T, Fukui M, Hasegawa G, Nakamura N, Ohta M, Obayashi H, Okanoue T
  • Journal Title: J Gastroenterol Volume: 46 Issue: 1 Pages: 101-107
  • DOI: 10.1007/s00535-010-0291-8
• [Journal Article] Simple formula to predict response to peginterferon alpha2b and ribavirin combination therapy in genotype 1 chronic hepatitis C patients with high viral loads. (2011)
  • Author(s): Itoh Y, Nishimura T, Hashimoto H, Yamaguchi K, Niimi T, Yokomizo C, Fujii H, Minami M, Yasui K, Mitsuyoshi H, Okanoue T, Takehara T, Hiasa Y, Onji M, Yoshikawa T.
  • Journal Title: Hepatol Res Volume: 41 Issue: 2 Pages: 126-132
  • DOI: 10.1111/j.1872-034x.2010.00750.x
  • Peer Reviewed
• [Journal Article] Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in Japan. (2011)
  • Author(s): Okanoue T, Umemura A, Yasui K, Itoh Y.
  • Journal Title: J Gastroenterol Hepatol Volume: 26 Issue: s1 Pages: 153-162
  • DOI: 10.1111/j.1440-1746.2010.06547.x
  • Peer Reviewed
• [Presentation] Reduced expression of BRM in hepatocellular carcinoma (2014)
  • Author(s): Yasui K, Gen Y, Tomie A, Kitaichi T, Itoh Y
  • Organizer: Annual Meeting 2014 of the American Association for Cancer Research (AACR)
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-04-09
• [Presentation] SOX2 promotes tumor growth via activation of the PI3K/Akt/mTORC1 signaling pathway in esophageal squamous cell carcinoma (2014)
  • Author(s): Gen Y, Yasui K, Kitaichi T, Tomie A, Itoh Y
  • Organizer: Annual Meeting 2014 of the American Association for Cancer Research (AACR)
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-04-08
• [Presentation] Efficacy and safety of sorafenib in patients aged 80 years and older with advanced hepatocellular carcinoma (2013)
  • Author(s): Yasui K, Jo M, Nishimura T, Yamaguchi K, Sumida Y, Mitsuyoshi H, Minami M, Itoh Y
  • Organizer: 64th Annual Meeting of the American Association for the Study of Liver Disease (AASLD)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-11-05
• [Presentation] Regulation of miR-335 expression in association with methylation status of MEST promoter in hepatocellular carcinoma (2013)
  • Author(s): Dohi O, Yasui K, Jo M, Itoh Y
  • Organizer: 64th Annual Meeting of the American Association for the Study of Liver Disease (AASLD)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-11-01
• [Presentation] SOX2 promotes tumor growth via activation of PI3K/Akt/mTORC1 pathway in esophageal squamous cell carcinoma (2013)
  • Author(s): Yasuyuki Gen, Kohichiroh Yasui, Tomoko Kitaichi, Akira Tomie, Nobuhisa Yamada, , Yuji Naito, Toshikazu Yoshikawa, and Yoshito Itoh
  • Organizer: 第72回 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 肝細胞癌におけるmiR-335とホスト遺伝子MESTのエピジェネティックな発現制御 (2013)
  • Author(s): 土肥 統, 安居幸一郎, 玄 泰行, 城 正泰, 伊藤義人, 田中真二, 有井滋樹, 吉川敏一
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] 非アルコール性脂肪性肝疾患における肝線維化とPNPLA3遺伝子多型 (2013)
  • Author(s): 安居幸一郎、伊藤義人、岡上 武
  • Organizer: 第99回 日本消化器病学会総会
  • Place of Presentation: 鹿児島
• [Presentation] SOX2は食道扁平上皮癌において、PI3K/AKT/mTOR経路を介して腫瘍増殖を促進する (2012)
  • Author(s): 玄 泰行、安居幸一郎、山田展久、和田貴子、土肥 統、内藤裕二、谷脇雅史、吉川敏一
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 肝細胞癌における新規メチル化遺伝子AKR1B1の同定 (2012)
  • Author(s): 山田展久、安居幸一郎、玄 泰行、遠藤美生、辻 和宏、土肥 統、赤澤貴子、小西知佳、冨江 晃、内藤裕二、田中真二、有井滋樹、吉川敏一
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 肝癌におけるEVI1の遺伝子増幅と発現亢進 (2012)
  • Author(s): 小西知佳、安居幸一郎、遠藤美生、玄 泰行、辻 和宏、土肥 統、赤澤貴子、山田展久 、内藤裕二、田中真二、有井滋樹、吉川敏一
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 胆道癌における新規欠失遺伝子PHF14 (2012)
  • Author(s): 赤澤貴子、安居幸一郎、玄 泰行、山田展久、遠藤美生、小西知佳、土肥 統、八 木信明、内藤裕二、吉川敏一
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 肝細胞癌におけるmiR-335とそのhost geneであるMESTのエピジェネティックな発現制御 (2012)
  • Author(s): 土肥 統、安居幸一郎、玄 泰行、遠藤美生、辻 和宏、小西知佳、和田貴子、山田展久、高田 久、内藤裕二、田中真二、有井滋樹、吉川 敏一
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 肝細胞癌を発症したNASH患者の臨床病理学的特徴―厚労省NASH班研究から― (2012)
  • Author(s): 安居幸一郎、橋本悦子、徳重克年、小森園康二、小池和彦、有井滋樹、今井康陽、島 俊英、寒原芳浩、西原利治、森 敬弘、河田純男、宇都浩文、高見史朗、角田圭雄、篁 俊成、川中美和、岡上 武
  • Organizer: 第48回 日本肝臓学会総会
  • Place of Presentation: 金沢
• [Presentation] SOX2は食道扁平上皮癌においてPI3K/Akt経路の活性化を介して、腫瘍形成を促進する (2011)
  • Author(s): 玄泰行、安居幸一郎、山田展久、和田貴子、内藤裕二、谷脇雅史、吉川敏一
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 肝細胞癌におけるtranscriptional cofactor P300の役割 (2011)
  • Author(s): 横溝千尋、山口寛二、西村健、光吉博則、安居幸一郎、南祐仁、岩井眞樹、伊藤義人、吉川敏一
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] ソラフェニブによる抗腫瘍効果の検討 (2011)
  • Author(s): 片山貴之、安居幸一郎、横溝千尋、西村健、遠藤美生、岡田頼久、山口寛二、光吉博則、南祐仁、岩井眞樹、伊藤義人、吉川敏一
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] 肝細胞癌に対するソラフェニブ治療の実態と有効性・安全性の検討―多施設共同研究― (2011)
  • Author(s): 片山貴之、安居幸一郎、角田圭雄、城正泰、木村浩之、高見史郎、新美敏久、藤井秀樹、中村英樹、世古口悟、益澤明、藤井恒太ら
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
• [Book] Non-Alcoholic Fatty Liver Disease in Japan, in Non-Alcoholic Fatty Liver Disease: A Practical Guide (2013)
  • Author(s): Okanoue, T., Yasui, K. and Itoh, Y.
  • Total Pages: 324
  • Publisher: Wiley-Blackwell
• [Remarks]
  • URL: http://www.f.kpu-m.ac.jp/k/sun/