Role of Epac in bladder cancer

• Project/Area Number: 15K20095
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Tokyo Medical and Dental University (2016-2017); Kyushu University (2015)
• Principal Investigator: ITSUMI Momoe 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (40585890)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 膀胱癌 / 遊走能 / 膀胱がん / EPAC1 / 移動性

Outline of Final Research Achievements

We report that EPAC1 and EPAC2 expression levels were significantly lower in bladder cancer tissue than in normal bladder tissue. In addition, bladder cancer cell lines showed reduced EPAC1 mRNA expression. Furthermore, EPAC1 overexpression in bladder cancer cell lines induced morphologic changes and markedly suppressed cell migration without affecting cell viability. The overexpressed EPAC1 preferentially localized at cell-cell interfaces. In conclusion, reduced EPAC1 expression in bladder tumors and poor migration of EPAC1-overexpressing cells implicate EPAC1 as an inhibitor of bladder cancer cell migration.

Research Products

• [Journal Article] Overexpression of exchange protein directly activated by cAMP-1 (EPAC1) attenuates bladder cancer cell migration (2018)
  • Author(s): Ichikawa Hirona、Itsumi Momoe、Kajioka Shunichi、Maki Tomoko、Lee Ken、Tomita Makoto、Yamaoka Shoji
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 495 Issue: 1 Pages: 64-70
  • DOI: 10.1016/j.bbrc.2017.10.142
• [Journal Article] A20 restores phorbol ester-induced differentiation of THP-1 cells in the absence of nuclear factor-κB activation (2017)
  • Author(s): Osako Miho、Itsumi Momoe、Yamaguchi Haruka、Takeuchi Hiroaki、Yamaoka Shoji
  • Journal Title: Journal of Cellular Biochemistry Volume: 119 Issue: 2 Pages: 1475-1487
  • DOI: 10.1002/jcb.26308
• [Journal Article] Glutathione Primes T Cell Metabolism for Inflammation (2017)
  • Author(s): Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, Binsfeld C, Hao Z, Brustle A, Itsumi M, Jager C, Chen Y, Pinkenburg O, Camara B, Ollert M, Bindslev-Jensen C, Vasiliou V, Gorrini C, Lang PA, Lohoff M, Harris IS, Hiller K, Brenner D.
  • Journal Title: Immunity Volume: 46 Issue: 4 Pages: 675-689
  • DOI: 10.1016/j.immuni.2017.03.019
• [Journal Article] Gene polymorphisms in antioxidant enzymes correlate with the efficacy of androgen-deprivation therapy for prostate cancer with implications of oxidative stress. (2017)
  • Author(s): Shiota M, Fujimoto N, Itsumi M, Takeuchi A, Inokuchi J, Tatsugami K, Yokomizo A, Kajioka S, Uchiumi T, Eto M.
  • Journal Title: Annals of oncology Volume: 28(3) Issue: 3 Pages: 569-575
  • DOI: 10.1093/annonc/mdw646
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Potential Role for YB-1 in Castration-Resistant Prostate Cancer and Resistance to Enzalutamide Through the Androgen Receptor V7. (2016)
  • Author(s): Shiota M, Fujimoto N, Imada K, Yokomizo A, Itsumi M, Takeuchi A, Kuruma H, Inokuchi J, Tatsugami K, Uchiumi T, Oda Y, Naito S.
  • Journal Title: J Natl Cancer Inst. Volume: 108 Issue: 7 Pages: djw005-djw005
  • DOI: 10.1093/jnci/djw005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epithelial to Mesenchymal Transition in Clear Cell Renal Cell Carcinoma with Rhabdoid Features. (2016)
  • Author(s): Sugimoto M, Kohashi K, Itsumi M, Shiota M, Abe T, Yamada Y, Kuroiwa K, Naito S, Oda Y.
  • Journal Title: Pathobiology. Volume: 83 Issue: 6 Pages: 277-286
  • DOI: 10.1159/000445752
  • Peer Reviewed
• [Journal Article] Equol inhibits prostate cancer growth via degradation of the androgen receptor by Skp2. (2016)
  • Author(s): Itsumi M, Shiota M, Takeuchi A, Kashiwagi E, Inokuchi J, Tatsugami K, Kajioka S, Uchiumi T, Naito S, Eto M, Yokomizo A.
  • Journal Title: Cancer Science Volume: ◯◯ Issue: 7 Pages: 1022-1028
  • DOI: 10.1111/cas.12948
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MP62-20 CROSSTALK BETWEEN EPITHELIAL-MESENCHYMAL TRANSITION AND CASTRATION RESISTANCE IN PROSTATE CANCER (2016)
  • Author(s): Masaki Shiota, Momoe Itsumi, Ario Takeuchi, Kenjiro Imada, Akira Yokomizo, Hidetoshi Kuruma, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, Seiji Naito, Masatoshi Eto
  • Journal Title: The Journal of Urology Volume: 195
  • Peer Reviewed
• [Journal Article] Actions of cAMP on calcium sensitization in human detrusor smooth muscle contraction. (2016)
  • Author(s): Hayashi M, Kajioka S, Itsumi M, Takahashi R, Shahab N, Ishigami T, Takeda M, Masuda N, Yamaguchi A, Naito S.
  • Journal Title: British Journal of Urology International Volume: 117 (1) Issue: 1 Pages: 179-191
  • DOI: 10.1111/bju.13180
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Crosstalk between epithelial-mesenchymal transition and castration resistance mediated by Twist1/AR signaling in prostate cancer (2015)
  • Author(s): Masaki Shiota, Momoe Itsumi, Ario Takeuchi, Kenjiro Imada, Akira Yokomizo, Hidetoshi Kuruma, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, Seiji Naito
  • Journal Title: Endocrine-related cancer Volume: 22 Issue: 6 Pages: 889-900
  • DOI: 10.1530/erc-15-0225
  • Peer Reviewed
• [Journal Article] Idh1 protects murine hepatocytes from endotoxin-induced oxidative stress by regulating the intracellular NADP+/NADPH ratio (2015)
  • Author(s): M Itsumi, S Inoue, AJ Elia, K Murakami, M Sasaki, EF Lind, D Brenner, IS Harris, IIC Chio, S Afzal, RA Cairns, DW Cescon, AR Elford, J Ye, PA Lang, WY Li, A Wakeham, GS Duncan, J Haight, A You-Ten, B Snow, K Yamamoto, PS Ohashi, TW Mak
  • Journal Title: Cell Death & Differentiation Volume: 22 Issue: 11 Pages: 1837-1845
  • DOI: 10.1038/cdd.2015.38
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Role for linear ubiquitination in the growth of HTLV-I-infected cells. (2017)
  • Author(s): Momoe Itsumi, Kazuhiro Iwai, Shoji Yamaoka.
  • Organizer: 第 18回国際ヒトレトロウイルス HTLV会議
  • Place of Presentation: ホテルグランアーク半蔵門、東京都千代田区
  • Year and Date: 2017-03-07
  • Int'l Joint Research
• [Presentation] EPAC1 suppresses migration of bladder cancer cells. (2017)
  • Author(s): Hirona Ichikawa, Shoji Yamaoka, Shunichi Kajioka, Momoe Itsumi
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] LUBAC構成分子HOIL-1Lの発現低下によるHTLV-I感染細胞の増殖抑制メカニズム (2017)
  • Author(s): 逸見百江、山岡昇司
  • Organizer: 第4回日本HTLV-1学会学術集会
• [Presentation] Serotonin receptor antagonist inhibits prostate cancer progression. (2016)
  • Author(s): Momoe Itsumi, Masaki Shiota, Akira Yokomizo, Eiji Kashiwagi, Ario Takeuchi, Kenjiro Imada, Katsunori Tatsugami, Junichi Inokuchi, Takeshi Uchiumi, Shunichi Kajioka, Seiji Naito, Masatoshi Etoh.
  • Organizer: The 75th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2016-10-06
  • Int'l Joint Research
• [Presentation] LUBAC構成分子HOIL-1Lの発現低下はHTLV-I感染細胞の増殖を抑制する (2016)
  • Author(s): 逸見百江、岩井一宏、山岡昇司.
  • Organizer: 第3回日本HTLV-1学会学術集会
  • Place of Presentation: 鹿児島市町村自治会館4階、鹿児島県鹿児島市
  • Year and Date: 2016-08-26
• [Presentation] 前立腺癌の増殖抑制を誘導するイソフラボンの作用機序 (2016)
  • Author(s): 逸見百江、塩田正己、武内在雄、柏木英二、猪口淳一、立神勝則、梶岡俊一、内海健、内藤誠二、江藤正俊、横溝晃.
  • Organizer: 第27回日本生体防御学会学術総会
  • Place of Presentation: 九州大学病院キャンパス内コラボステーション１視聴覚ホール、福岡県福岡市
  • Year and Date: 2016-07-07
• [Presentation] Idh1 protects murine hepatocytes from endotoxin induced oxidative stress (2015)
  • Author(s): ITSUMI Momoe, INOUE Satoshi, ELIA Andrew J., MURAKAMI Kiichi, LIND Evan F., BRENNER Dirk , HARRIS Isaac S., CHIO Iok In Christine, Cescon David, CAIRNS Rob A., OHASHI Pamela S., MAK Tak W.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-18
  • Int'l Joint Research
• [Presentation] Equol promotes protein degradation of androgen receptor via Skp2 and suppresses cell proliferation in prostate cancer (2015)
  • Author(s): Momoe Itsumi, Masaki Shiota, Akira Yokomizo, Eiji Kashiwagi, Ario Takeuchi, Kenjiro Imada, Katsunori Tatsugami, Junichi Inokuchi, Takeshi Uchiumi, Shunichi Kajioka, Seiji Naito
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
  • Int'l Joint Research