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

2013 Fiscal Year Final Research Report

• 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
• 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

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] 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 Pages: 1849-1853
  • DOI: 10.3892/ol.2013.1278
• [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 Pages: 810-816
  • DOI: 10.1111/cas.12155
• [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 Pages: 1093-1099
  • DOI: 10.1111/hepr.12059
• [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 Pages: 301-311
  • DOI: 10.1111/liv.12033
• [Journal Article] Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma (2013)
  • Author(s): Dohi O, Yasui K, Gen Y, Takada H, Endo M, Tsuji K, Konishi C, Yamada N, Mitsuyoshi H, Yagi N, Naito Y, Tanaka S, Arii S, Yoshikawa T
  • Journal Title: Int J Oncol Volume: 42 Pages: 411-418
  • DOI: 10.3892/ijo.2012.1724
• [Journal Article] Alterations of the SWI/SNF chromatin remodelling subunit-BRG1 and BRM in hepatocellular carcinoma (2013)
  • Author(s): Endo M, Yasui K, Zen Y, Gen Y, Zen K, Tsuji K, Dohi O, Mitsuyoshi H, Tanaka S, Taniwaki M, Nakanuma Y, Arii S, Yoshikawa T
  • Journal Title: Liver Int Volume: 33 Pages: 105-117
  • DOI: 10.1111/liv.12005
• [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 Pages: 515-525
  • DOI: 10.1007/s00535-012-0653-5
• [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 Pages: 1407-1415
  • DOI: 10.1002/hep.25956
• [Journal Article] The Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD). 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, Sumida Y, Umemura A, Matsuo K, Takahashi M, Takamura T, Yasui K, Saibara T, Hashimoto E, Kawanaka M, Watanabe S, Kawata S, Imai Y, Kokubo M, Shima T, Park H, Tanaka H, Tajima K, Yamada R, Matsuda F, Okanoue T
  • Journal Title: PLoS One Volume: 7 Pages: e38322
  • DOI: 10.1371/journal.pone.0038322
• [Journal Article] Clinical and pathological progression of nonalcoholic 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 Pages: 767-773
  • DOI: 10.1111/j.1872-034X.2012.00986.x
• [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 Pages: 140-147
  • DOI: 10.1016/j.canlet.2011.06.030
• [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 Pages: 809-821
  • DOI: 10.1007/s00535-011-0392-z
• [Journal Article] Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma (2011)
  • Author(s): Yasui K, Hashimoto E, Komorizono Y, Koike K, Arii S, Imai Y, Shima T, Kanbara Y, Saibara T, Mori T, Kawata S, Uto H, Takami S, Sumida Y, Takamura T, Kawanaka M, Okanoue T, and The Japan NASH Study Group, The Ministry of Health, Labour and Welfare of Japan
  • Journal Title: Clin Gastroenterol Hepatol Volume: 9 Pages: 428-433
  • DOI: 10.1016/j.cgh.2011.01.023
• [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 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 Pages: 836-842
  • DOI: 10.1111/j.1440-1746.2010.06568.x
• [Journal Article] Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD). A simple clinical scoring system using ferritin, fasting insulin, and type IV collagen 7S for predicting steatohepatitis in nonalcoholic fatty liver disease (2011)
  • Author(s): Sumida Y, Yoneda M, Hyogo H, Yamaguchi K, Ono M, Fujii H, Eguchi Y, Suzuki Y, Imai S, Kanemasa K, Fujita K, Chayama K, Yasui K, Saibara T, Kawada N, Fujimoto K, Kohgo Y, Okanoue T
  • Journal Title: J Gastroenterol Volume: 46 Pages: 257-268
  • DOI: 10.1007/s00535-010-0305-6
• [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 Pages: 101-107
  • DOI: 10.1007/s00535-010-0291-8
• [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