Identification of host cell factors involved in diphtheria toxin sensitivity by using shRNA library.

• Project/Area Number: 20390127
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Osaka University
• Principal Investigator: MEKADA Eisuke 大阪大学, 微生物病研究所, 教授 (20135742)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000); Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: ジフテリア毒素 / shRNA / エンドサイトーシス / 宿主因子 / 網羅的遺伝子同定法 / 宿主側因子 / 綱羅的遺伝子同定法 / ジフラリア毒素 / コレステロール

Research Abstract

We performed a large scale screening of genes encoding host cell factors involved in cell sensitivity to diphtheria toxin by using shRNA library. Total 11 genes were identified as genes which are possibly involved in DT sensitivity. Among them, genes encoding enzymes in cholesterol biosynthesis pathway were confirmed to be involved in DT sensitivity.

Research Products

• [Journal Article] Development of anti-HB-EGFimmunoliposomes for the treatment ofbreast cancer (2012)
  • Author(s): Nishikawa K, Asai T, Shigematsu H, Shimizu K, Kato H, Asano Y, Takashima S, Mekada E, Oku N, Minamino T.
  • Journal Title: J Control Release Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] MIG-13 controls anteroposterior cellmigration by interacting withUNC-71/ ADM-1 and SRC-1 incaenorhabditis elegans (2012)
  • Author(s): Masuda H, Nakamura K, Takata N, Ito B, Hirose T, Moribe H, Mekada E, Okada M
  • Journal Title: FEBS Letters Volume: 586 Pages: 740-746
  • Peer Reviewed
• [Journal Article] Development of anti-HB-EGF immunoliposomes for the treatment of breast cancer (2012)
  • Author(s): Nishikawa K, Asai T, Mekada E, 他7名
  • Journal Title: J Control Release Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] MIG-13 controls anteroposterior cell migration by interacting with UNC-71/ADM-1 and SRC-1 in caenorhabditis elegans (2012)
  • Author(s): Masuda H, Nakamura K, Mekada E, 他5名
  • Journal Title: FEBS Letters Volume: 586 Pages: 740-746
  • Peer Reviewed
• [Journal Article] HB-EGF and PDGF mediate reciprocalinteractions of carcinoma cells withcancer-associated fibroblasts tosupport progression of uterine cervicalcancers (2011)
  • Author(s): Murata T, Mizushima H, Chinen I, Moribe H, Yagi S, Hoffman RM, Kimura T, Yoshino K, Ueda Y, Enomoto T, Mekada E
  • Journal Title: Cancer Research Volume: 71 Pages: 6633-6642
  • Peer Reviewed
• [Journal Article] A novelanti-human HB-EGF monoclonal antibodywith multiple antitumor mechanismsagainst ovarian cancer cells. (2011)
  • Author(s): Miyamoto S, Iwamoto R, Furuya A, Takahashi K, Sasaki Y, Ando H, YotsumotoF, Yoneda T, Hamaoka M, Yagi H, MurakamiT, Hori S, Shitara K, Mekada E
  • Journal Title: Clinical Cancer Research Volume: 17 Pages: 6733-6741
  • Peer Reviewed
• [Journal Article] Assessment ofHB-EGF levels in peritoneal fluid andserum of ovarian cancer patients usingELISA (2011)
  • Author(s): Hikita S, Yotsumoto F, Fukami T, Horiuchi S, Sanui A, Miyata K, Nam SO, Tsujioka H, Ueda T, Shirota K, YoshizatoT, Maeda K, Ishikawa T, Okuno Y, Kuroki M, Mekada E, Miyamoto S
  • Journal Title: Anticancer Res Volume: 31 Pages: 2553-2559
  • Peer Reviewed
• [Journal Article] Proteolytic activation of heparinbinding EGF-like growth factor bymembrane-type matrix metalloproteinase-1 in ovarian carcinoma cells (2011)
  • Author(s): Koshikawa N, Mizushima H, Minegishi T, Eguchi F, Yotsumoto F, Nabeshima K, Miyamoto S, Mekada E, Seiki M.
  • Journal Title: Cancer Science Volume: 102 Pages: 111-116
  • Peer Reviewed
• [Journal Article] HB-EGF and PDGF Mediate Reciprocal Interactions of Carcinoma Cells with Cancer-Associated Fibroblasts to Support Progression of Uterine Cervical Cancers (2011)
  • Author(s): Murata T, Mizushima H, Mekada E, 他8名
  • Journal Title: Cancer Research Volume: 71 Pages: 6633-6642
  • Peer Reviewed
• [Journal Article] A Novel Anti-Human HB-EGF Monoclonal Antibody with Multiple Antitumor Mechanisms against Ovarian Cancer Cells (2011)
  • Author(s): Miyamoto S, Iwamoto R, Mekada E, 他11名
  • Journal Title: Clinical Cancer Research Volume: 17 Pages: 6733-6741
  • Peer Reviewed
• [Journal Article] Assessment of HB-EGF levels in peritoneal fluid and serum of ovarian cancer patients using ELISA (2011)
  • Author(s): Hikita S, Yotsumoto F, Mekada E, 他14名
  • Journal Title: Anticancer Research Volume: 31 Pages: 2553-2559
  • Peer Reviewed
• [Journal Article] Proteolytic activation of heparin-binding EGF-like growth factor by membrane-type matrix metlloproteinase-1 in ovarian carcinoma cells (2011)
  • Author(s): Koshikawa N, Mizushima H, Mekada E, 他6名
  • Journal Title: Cancer Science Volume: 102 Pages: 111-116
  • Peer Reviewed
• [Journal Article] MT1-MMP cleaves off the NH2-terminal portion of HB-EGF and converts it into a heparin-independent growth factor (2010)
  • Author(s): Koshikawa N, Mizushima H, Minegishi T, Iwamoto R, Mekada E, Seiki M
  • Journal Title: Cancer Res Volume: 70 Pages: 6093-6103
  • Peer Reviewed
• [Journal Article] HB-EGF function incardiac valve development requires interaction with heparan sulfate proteoglycans (2010)
  • Author(s): Iwamoto R, Mine N, Kawaguchi T, MinamiS, Saeki K, Mekada E.
  • Journal Title: Development Volume: 137 Pages: 2205-2214
  • Peer Reviewed
• [Journal Article] Anti-human HB-EGF monoclonal antibodies inhibiting ectodomain shedding of HB-EGF and diphtheria toxin binding. (2010)
  • Author(s): Hamaoka M, Chinen I, Murata T, Takashima S, Iwamoto R, Mekada E
  • Journal Title: J. Biochem Volume: 148 Pages: 55-69
  • NAID: 10027877136
  • Peer Reviewed
• [Journal Article] HumanizedGene Replacement in Mice Reveals theContribution of Cancer Stroma-DerivedHB-EGF to Tumor Growth (2010)
  • Author(s): Ichise T, Adachi S, Ohishi M, Ikawa M, Okabe M, Iwamoto R, Mekada E
  • Journal Title: Cell StructFunct Volume: 35 Pages: 3-13
  • Peer Reviewed
• [Journal Article] HB-EGF function in cardiac valve development requires interaction with heparan sulfate proteoglycans (2010)
  • Author(s): Iwamoto R, Mine N, Mekada E, 他3名
  • Journal Title: Development Volume: 137 Pages: 2205-2214
  • Peer Reviewed
• [Journal Article] Anti-human HB-EGF monoclonal antibodies inhibiting ectodomain shedding of HB-EGF and diphtheria toxin binding (2010)
  • Author(s): Hamaoka M, Chinen I, Mekada E, 他3名
  • Journal Title: J.Biochem. Volume: 148 Pages: 55-69
  • NAID: 10027877136
  • Peer Reviewed
• [Journal Article] Humanizad Gene Replacement in Mice Reveals the Contribution of Cancer Stroma-Derived HB-EGF to Tumor Growth. (2010)
  • Author(s): Ichise T, Adachi S, Ohishi M, Ikawa M, Okabe M, Iwamoto R, Mekada E.
  • Journal Title: Cell Struct Funct. Volume: 35 Pages: 3-13
  • Peer Reviewed
• [Journal Article] Anti-human HB-EGF monoclonal antibodies inhibiting ectodomain shedding of HB-EGF and diphtheria toxin binding. (2010)
  • Author(s): Hamaoka, M., Chinen, I., Murata, T., Takashima, S., Iwamoto, R., Mekada, E.
  • Journal Title: J.Biochem. Volume: 148 Pages: 55-69
  • NAID: 10027877136
  • Peer Reviewed
• [Journal Article] Integrin signal masksgrowth-promotion activity of HB-EGF inmonolayer cell cultures. (2009)
  • Author(s): Mizushima H, Wang X, Miyamoto S, Mekada E.
  • Journal Title: J. Cell Sci Volume: 122 Pages: 4277-4286
  • Peer Reviewed
• [Journal Article] Synergistic antitumor effect ofpaclitaxel with CRM197, an inhibitor of HB-EGF, in ovarian cancer (2009)
  • Author(s): Yagi H, Yotsumoto F, Sonoda K, Kuroki M, Mekada E, Miyamoto S
  • Journal Title: Int J Cancer Volume: 124 Pages: 1429-1439
  • Peer Reviewed
• [Journal Article] Synergistic antitumor effect of paclitaxel with CRM197, an inhibitor of HB-EGF, in ovarian cancer. (2009)
  • Author(s): Yagi H, Yotsumoto F, Sonoda K, Kuroki M, Mekada E, Miyamoto S
  • Journal Title: Int J Cancer Volume: 124 Pages: 1429-1439
  • Peer Reviewed
• [Journal Article] Integrin signal masks growth-promotion activity of HB-EGF in monolayer cell cultures. (2009)
  • Author(s): Mizushima, H., Wang, X., Miyamoto, S., Mekada, E.
  • Journal Title: J Cell Sci. Volume: 122 Pages: 4277-4286
  • Peer Reviewed
• [Journal Article] UCSD-Nature Molecule Pages (2008)
  • Author(s): Mekada E, Iwamoto R. HB-EGF
  • Journal Title: Publishedonline
  • DOI: 10.1038/mp.a002932.01
  • Peer Reviewed
• [Journal Article] Heparin-binding epidermal growth factor-likegrowth factor as a new target moleculefor cancer therapy (2008)
  • Author(s): Miyamoto S, Yagi H, Yotsumoto F, Kawarabayashi T, Mekada E
  • Journal Title: Adv Exp Med Biol Volume: 622 Pages: 281-295
  • Peer Reviewed
• [Journal Article] Thefusing ability of sperm is bestowed byCD9-containing vesicles released fromeggs in mice (2008)
  • Author(s): Miyado K, Yoshida K, Yamagata K, Sakakibara K, Okabe M, Wang X, MiyamotoK, Akutsu H, Kondo T, Takahashi Y, BanT, Ito C, Toshimori K, Nakamura A, ItoM, Miyado M, Mekada E, Umezawa A
  • Journal Title: Proc Natl Acad Sci USA Volume: 105 Pages: 12921-12926
  • Peer Reviewed
• [Journal Article] Double deficiency oftetraspanins CD9 and CD81 alters cellmotility and protease production of macrophages and causes COPD-likephenotype in mice (2008)
  • Author(s): Takeda Y, He P, Tachibana I, Zhou B, Miyado K, Kaneko H, Suzuki M, Minami S, Iwasaki T, Goya S, Kijima T, Kumagai T, Yoshida M, Osaki T, Komori T, Mekada E, Kawase I.
  • Journal Title: J Biol Chem Volume: 283 Pages: 26089-26097
  • Peer Reviewed
• [Journal Article] Possible involvement of CD81 in acrosome reaction of sperm inmice (2008)
  • Author(s): Tanigawa M, Miyamoto K, KobayashiS, Sato M, Akutsu H, Okabe M, MekadaE, Sakakibara K, Miyado M, Umezawa A, Miyado K
  • Journal Title: Mol Reprod Dev Volume: 75 Pages: 150-155
  • Peer Reviewed
• [Journal Article] HB-EGF decelerates cell proliferation synergistically with TGF-a in perinataldistal lung development (2008)
  • Author(s): Minami S, Iwamoto R, Mekada E.
  • Journal Title: Dev. Dyn Volume: 237 Pages: 247-258
  • Peer Reviewed
• [Journal Article] Validation of HB-EGF and amphiregulin astargets for human cancer therapy. (2008)
  • Author(s): Yotsumoto F, Yagi H, Suzuki SO, Oki E, Tsujioka H, Hachisuga T, Sonoda K, Kawarabayashi T, Mekada E, Miyamoto S.
  • Journal Title: Biochem Biophys Res Commun Volume: 365 Pages: 555-561
  • Peer Reviewed
• [Journal Article] HB-EGF decelerates cell proliferation synergistically with TGF-a in perinatal distal lung development. (2008)
  • Author(s): Minami, S., Iwamoto, R., Mekada, E.
  • Journal Title: Dev. Dyn. 237 Pages: 247-258
  • Peer Reviewed
• [Journal Article] Double deficiency of tetraspanins CD9 and CD81 alters cell motility and protease production of macrophages and causes COPD-1ike phenotype in mice. (2008)
  • Author(s): Takeda Y, He P, Tachibana I, Mekada, E, 他12名
  • Journal Title: J Biol Chem. 283 Pages: 26089-26097
  • Peer Reviewed
• [Journal Article] The fusing ability of sperm is bestowed by CD9-containing vesicles released from eggs in mice. (2008)
  • Author(s): Miyado K, Yoshida K, Mekada, E, 他15名
  • Journal Title: Proc Natl Acad Sci U S A. 105 Pages: 12921-12926
  • Peer Reviewed
• [Presentation] 目加田英輔子宮頚癌ではHB-EGFとPDGFを介して癌細胞と癌関連線維芽細胞が相互作用し、癌細胞の増殖を促進する (2011)
  • Author(s): 村田卓也、水島寛人、吉野潔、上田豊、榎本隆之、木村正
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] The role of tetraspanins in the dual oxidase system of C. elegansand humans (2011)
  • Author(s): Mekada E
  • Organizer: Membrane Organization by Molecular Scaffolds
  • Place of Presentation: Saxtons River, Vermont
• [Presentation] FAKのFERMドメインのリン酸化によるHB-EGF依存的細胞増殖制御 (2011)
  • Author(s): 水島寛人、船越敍希、目加田英輔
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
• [Presentation] HB-EGF細胞質内フラグメントは破骨細胞の分化を負に制御する (2011)
  • Author(s): 中村尚志、伊藤ちひろ、北川教弘、岩本亮、竹家達夫、目加田英輔
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
• [Presentation] テトラスパニンによる活性酸素産生の制御 (2011)
  • Author(s): 森部弘樹、小央良二、中村邦明、目加田英輔
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
• [Presentation] Clinical development of the diphtheria toxin mutant CRM197 forcancer therapy (2011)
  • Author(s): Mekada E
  • Organizer: ETOX15 European Workshop on Bacterial Protein Toxins
  • Place of Presentation: Oslo, Norway
• [Presentation] 子宮頚癌ではHB-EGFとPDGFを介して癌細胞と癌関連線維芽細胞が相互作用し、癌細胞の増殖を促進する (2011)
  • Author(s): 村田卓也、水島寛人、吉野潔、上田豊、榎本隆之、木村正、目加田英輔
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] The role of tetraspanins in the dual oxidase system of C.elegans and humans (2011)
  • Author(s): Mekada E
  • Organizer: FASEB Summer Research Conferences Membrane Organization by Molecular Scaffolds
  • Place of Presentation: Vermont Academy (U.S.A)(招待講演)
• [Presentation] FAKのFERMドメインのリン酸化によるHB-EGF依存的細胞増殖制御 (2011)
  • Author(s): 水島寛人、船越敍希、目加田英輔
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学
• [Presentation] HB-EGF細胞質内フラグメントは破骨細胞の分化を負に制御する (2011)
  • Author(s): 中村尚志、伊藤ちひろ、北川教弘、岩本亮、竹家達夫、目加田英輔
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学
• [Presentation] テトラスパニンによる活性酸素産生の制御 (2011)
  • Author(s): 森部弘樹、小央良二、中村邦明、目加田英輔
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学
• [Presentation] Clinical development of the diphtheria toxin mutant CRM197 for cancer therapy (2011)
  • Author(s): Mekada E
  • Organizer: ETOX15 European Workshop on Bacterial Protein Toxins
  • Place of Presentation: Soria Moria Hotel and Conference Centre, Oslo (Norway)
• [Presentation] HB-EGFの作用機構と癌分子標的としての解析 (2010)
  • Author(s): 目加田英輔
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] HB-EGFの作用機構と癌分子標的としての解析 (2010)
  • Author(s): 目加田英輔
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: リーガロイヤルホテル大阪
  • Year and Date: 2010-09-23
• [Presentation] FAKはHB-EGF依存的な細胞増殖に必要である (2010)
  • Author(s): 船越敍希、水島寛人、目加田英輔
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
• [Presentation] 癌随伴線維芽細胞はHB-EGFおよびPDGFを介して子宮頚癌細胞の増殖を促進する (2010)
  • Author(s): 村田卓也、水島寛人、榎本隆之、木村正目加田英輔
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
• [Presentation] HB-EGF-EGFRシグナルは多重の経路を介して骨芽細胞の分化を制御する (2010)
  • Author(s): 中村尚志、北川教弘、岩本亮、竹家達夫目加田英輔
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
• [Presentation] 線虫外骨格形成においてテトラスパニンにより制御される分子経路の同定 (2010)
  • Author(s): 森部弘樹、小央良二、中村邦明、目加田英輔
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
• [Presentation] HB-EGF is a novel therapeutic target for ovarian cancer : Development of an HB-EGF inhibitor as an anticancer drug (2010)
  • Author(s): Eisuke Mekada
  • Organizer: at 8th Joint Conference of the American Associationfor Cancer Research and the Japanese Cancer Association
  • Place of Presentation: Hawaii, USA
• [Presentation] FAKはHB-EGF依存的な細胞増殖に必要である (2010)
  • Author(s): 船越敍希、水島寛人、目加田英輔
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪国際会議場
• [Presentation] 癌随伴線維芽細胞はHB-EGFおよびPDGFを介して子宮頚癌細胞の増殖を促進する (2010)
  • Author(s): 村田卓也、水島寛人、榎本隆之、木村正、目加田英輔
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪国際会議場
• [Presentation] HB-EGF-EGFRシグナルは多重の経路を介して骨芽細胞の分化を制御する (2010)
  • Author(s): 中村尚志、北川教弘、岩本亮、竹家達夫、目加田英輔
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪国際会議場
• [Presentation] 線虫外骨格形成においてテトラスパニンにより制御される分子経路の同定 (2010)
  • Author(s): 森部弘樹、小央良二、中村邦明、目加田英輔
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪国際会議場
• [Presentation] インテグリンシグナルはEGFファミリー増殖因子の増殖因子活性を単層培養において不顕在化する (2009)
  • Author(s): 水島寛人、宮本新吾、目加田英輔
  • Organizer: 第61回日本細胞生物学会大会
  • Place of Presentation: 名古屋
• [Presentation] HB-EGFの生理機能発揮におけるエクトドメイン・シェディングの役割 (2008)
  • Author(s): 岩本亮、目加田英輔
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-29
• [Remarks]
  • URL: http://cell-biology.biken.osaka-u.ac.jp/MekadaLabHP/Home.html
• [Remarks]
  • URL: http://cell-biology.biken.osaka-u.ac.jp/MekadaLabHP/Home.html
• [Remarks]
  • URL: http://cell-biology.biken.osaka-u.ac.jp/MekadaLabHP/Home.html
• [Remarks]
  • URL: http://cell-biology,biken.osaka-u.ac.jp/MekadaLabHP/Home.html