Identification of novel genes responsible for malignant progression in renal cell cancer

• Project/Area Number: 15K08405
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Oita University
• Principal Investigator: Masatsugu Moriyama 大分大学, 医学部, 教授 (90239707)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 腎細胞癌 / 悪性化 / 責任遺伝子 / WDR20 / Sav1 / SAV1 / ノックアウトマウス / 腎癌

Outline of Final Research Achievements

We had identified the genes specifically down-regulated in malignant renal cell carcinomas. Among them, we focused on WDR20 and Sav1 genes and analyzed their functions in the renal cancer cells. When WDR20 gene were introduced into the cancer cells, cell growth was significantly inhibited and apoptosis was induced. Therefore, WDR20 would function as tumor suppressor gene in renal cell carcinomas.
We established a Sav1 conditional knockout mouse which lost Sav1 expression specifically in renal tubes. The mice showed hyperproliferation of renal tubes and variations in cell size and nuclear shape of the epithelium, suggesting that Sav1 is required for the maintenance of growth, nuclear size and structure of renal tubules under physiological conditions, and its deficiency leads to the acquisition of enhanced proliferation of renal epithelial cells.

Research Products

• [Journal Article] Downregulation of dual-specificity phosphatase 4 enhances cell proliferation and invasiveness in colorectal carcinomas (2017)
  • Author(s): Ichimanda Michihiro、Hijiya Naoki、Tsukamoto Yoshiyuki、Uchida Tomohisa、Nakada Chisato、Akagi Tomonori、Etoh Tsuyoshi、Iha Hidekatsu、Inomata Masafumi、Takekawa Mutsuhiro、Moriyama Masatsugu
  • Journal Title: Cancer Sci Volume: 109 Issue: 1 Pages: 250-258
  • DOI: 10.1111/cas.13444
  • Peer Reviewed / Open Access
• [Journal Article] A 17-molecule set as a predictor of complete response to neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in esophageal cancer (2017)
  • Author(s): Fujishima Hajime、Fumoto Shoichi、Shibata Tomotaka、Nishiki Kohei、Tsukamoto Yoshiyuki、Etoh Tsuyoshi、Moriyama Masatsugu、Shiraishi Norio、Inomata Masafumi
  • Journal Title: PLoS One Volume: 12 Issue: 11 Pages: e0188098-e0188098
  • DOI: 10.1371/journal.pone.0188098
  • Peer Reviewed / Open Access
• [Journal Article] Periportal lymphatic system on post-hepatobiliary phase Gd-EOB-DTPA-enhanced MR imaging in normal subjects and patients with chronic hepatitis C (2017)
  • Author(s): Yamada Yasunari、Matsumoto Shunro、Mori Hiromu、Takaji Ryo、Kiyonaga Maki、Hijiya Naoki、Tanoue Rika、Tomonari Kenichiro、Tanoue Shuichi、Hongo Norio、Ohta Masayuki、Seike Masataka、Inomata Masafumi、Murakami Kazunari、Moriyama Masatsugu
  • Journal Title: Abdom Radiol (NY) Volume: 42 Issue: 10 Pages: 2410-2419
  • DOI: 10.1007/s00261-017-1155-y
  • Peer Reviewed
• [Journal Article] Overexpression of cannabinoid receptor 1 in esophageal squamous cell carcinoma is correlated with metastasis to lymph nodes and distant organs, and poor prognosis. (2017)
  • Author(s): Hijiya N, Shibata T, Daa T, Hamanaka R, Uchida T, Matsuura K, Tsukamoto Y, Nakada C, Iha H, Inomata M, Moriyama M.
  • Journal Title: Pathol Int. Volume: 67 Issue: 2 Pages: 83-90
  • DOI: 10.1111/pin.12495
  • Peer Reviewed / Open Access
• [Journal Article] Periportal low attenuation associated with liver metastasis from colorectal cancer: evaluation using multi-detector-row CT with pathological correlation. 2017 Jan;35(1): (2017)
  • Author(s): Takaji R, Matsumoto S, Kiyonaga M, Yamada Y, Mori H, Iwashita Y, Ohta M, Inomata M, Hijiya N, Moriyama M, Takaki H, Fukuzawa K, Yonemasu H.
  • Journal Title: Jpn J Radiol. Volume: 35 Issue: 1 Pages: 10-15
  • DOI: 10.1007/s11604-016-0592-9
  • Peer Reviewed
• [Journal Article] Kidney-specific knockout of Sav1 in the mouse promotes hyper-proliferation of renal tubular epithelium through suppression of the Hippo pathway. (2016)
  • Author(s): Kai T, Tsukamoto Y, Hijiya N, Tokunaga A, Nakada C, Uchida T, Daa T, Iha H, Takahashi M, Nomura T, Sato F, Mimata H, Ikawa M, Seto M, Matsuura K, Moriyama M.
  • Journal Title: J Pathol. Volume: 印刷中 Issue: 1 Pages: 97-108
  • DOI: 10.1002/path.4706
  • Peer Reviewed / Open Access
• [Journal Article] Perirenal lymphatic systems: evaluation using spectral presaturation with inversion recovery T2-weighted MR images with 3D volume isotropic turbo spin-echo acquisition at 3.0-T (2016)
  • Author(s): Matsumoto S, Mori H, Kiyonaga M, Yamada Y, Takaji R, Hijiya N, Moriyama M, Tanoue R, Matsumoto T, Hasebe T
  • Journal Title: Journal of Magnetic Resonance Imaging Volume: 00 Issue: 4 Pages: 00-00
  • DOI: 10.1002/jmri.25244
  • Peer Reviewed / Open Access
• [Journal Article] Atrial Fibrillation-Mediated Upregulation of miR-30d Regulates Myocardial Electrical Remodeling of the G-Protein-Gated K⁺ Channel, <i>I</i>_K.ACh (2016)
  • Author(s): Morishima M, Iwata E, Nakada C, Tsukamoto Y, Takanari H, Miyamoto S, Moriyama M, Ono K
  • Journal Title: Circulation Journal Volume: 80 Issue: 6 Pages: 1346-1355
  • DOI: 10.1253/circj.CJ-15-1276
  • NAID: 130005153582
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] Reduced phosphorylation of ribosomal protein S6 is associated with sensitivity to MEK inhibition in gastric cancer cells. (2016)
  • Author(s): Hirashita Y, Kodama M, Okimoto T, Murakami K, Moriyama M, et al.
  • Journal Title: Cancer Science Volume: 107(12) Issue: 12 Pages: 1919-1928
  • DOI: 10.1111/cas.13094
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Downregulation of WDR20 due to loss of 14q is involved in the malignant transformation of clear cell renal cell carcinoma. (2016)
  • Author(s): Takahashi M, Tsukamoto Y, Kai T, Tokunaga A, Nakada C, Hijiya N, Uchida T, Daa T, Nomura T, Sato F, Mimata H, Matsuura K, Moriyama M.
  • Journal Title: Cancer Science Volume: 107(4) Issue: 4 Pages: 417-423
  • DOI: 10.1111/cas.12892
  • Peer Reviewed / Open Access
• [Journal Article] An 80-gene set to predict response to preoperative chemoradiotherapy for rectal cancer by principle component analysis. (2016)
  • Author(s): Empuku S, Nakajima K, Akagi T, Kaneko K, Hijiya N, Etoh T, Shiraishi N, Moriyama M, Inomata M.
  • Journal Title: Mol Clin Oncol. Volume: 4 Pages: 733-739
  • Peer Reviewed
• [Journal Article] Genomic loss of DUSP4 contributes to the progression of intraepithelial neoplasm of pancreas to invasive carcinoma. (2016)
  • Author(s): Hijiya N, Tsukamoto Y, Nakada C, Tung NL, Kai T, Matsuura K, Shibata K, Inomata M, Uchida T, Tokunaga A, Amada K, Shirao K, Yamada Y, Mori H, Takeuchi I, Seto M, Aoki M, Takekawa M, Moriyama M.
  • Journal Title: Cancer Res. Volume: 76 Issue: 9 Pages: 2612-2625
  • DOI: 10.1158/0008-5472.can-15-1846
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Glucose Fluctuations Aggravate Cardiac Susceptibility to Ischemia/Reperfusion Injury by Modulating MicroRNAs Expression (2016)
  • Author(s): Saito S, Thuc LC, Teshima Y, Nakada C, Nishio S, Kondo H, Fukui A, Abe I, Ebata Y, Saikawa T, Moriyama M, Takahashi N.
  • Journal Title: Circulation Journal Volume: 80 Issue: 1 Pages: 186-195
  • DOI: 10.1253/circj.CJ-14-1218
  • NAID: 130005116977
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] Expression of DDX27 contributes to colony-forming ability of gastric cancer cells and correlates with poor prognosis in gastric cancer. (2015)
  • Author(s): Tsukamoto Y, Fumoto S, Noguchi T, Yanagihara K, Hirashita Y, Nakada C, Hijiya N, Uchida T, Matsuura K, Hamanaka R, Murakami K, Seto M, Inomata M, Moriyama M.
  • Journal Title: Am J Cancer Res. Volume: 5 Pages: 2998-3014
  • Peer Reviewed
• [Journal Article] Helicobacter pylori Infection in Thailand: A Nationwide Study of the CagA Phenotype. (2015)
  • Author(s): Uchida T, Miftahussurur M, Pittayanon R, Vilaichone RK, Wisedopas N, Ratanachu-Ek T, Kishida T, Moriyama M, Yamaoka Y, Mahachai V.
  • Journal Title: PLoS One. Volume: 10 Issue: 9 Pages: e0136775-e0136775
  • DOI: 10.1371/journal.pone.0136775
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 大腸癌におけるDUSP4発現低下は増殖能・浸潤能に関与する (2017)
  • Author(s): 一万田 充洋, 泥谷 直樹, 塚本 善之, 中田 知里, 衛藤 剛, 伊波 英克, 猪股 雅史, 守山 正胤
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 泌尿器科がん研究の最前線 高異型度淡明腎細胞癌におけるHippoシグナルの重要性 (2017)
  • Author(s): 守山 正胤, 甲斐 友喜, 松浦 恵子, 野村 威雄, 佐藤 文憲, 三股 浩光, 高橋 美香
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 中年男性において破裂を契機に発見された膵粘液性嚢胞性腫瘍の一例 (2017)
  • Author(s): 清永 麻紀, 山田 康成, 松本 俊郎, 高司 亮, 森 宣, 矢田 一宏, 太田 正之, 猪股 雅史, 泥谷 直樹, 守山 正胤
  • Organizer: 第53回日本医学放射線学会秋季臨床大会
• [Presentation] From Bench to Bedside 臨床と基礎の連携研究 食道がん化学療法におけるトランスレーショナルリサーチ (2017)
  • Author(s): 麓 祥一, 錦 耕平, 藤島 紀, 柴田 智隆, 衛藤 剛, 白石 憲男, 守山 正胤, 猪股 雅史
  • Organizer: 第42回日本外科系連合学会学術集会
• [Presentation] 選択的血漿交換療法 エバキュア2Aを用いたサイトカイン除去 (2016)
  • Author(s): 内田 智久, 中嶋 桃子, 友 雅司, 泥谷 直樹, 守山 正胤
  • Organizer: 第37回日本アフェレシス学会学術大会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-11-25
  • Invited
• [Presentation] DUSP4の発現低下は膵上皮内癌から浸潤癌への進展に関与する (2016)
  • Author(s): 泥谷 直樹, 塚本 善之, 中田 知里, 甲斐 友喜, 松浦 恵子, 猪股 雅史, 白尾 國昭, 森 宣, 瀬戸 加大, 青木 正博, 武川 睦寛, 守山 正胤
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-10-06
• [Presentation] Identification of WDR20 as a new tumor suppressor gene preferentially altered in high-grade clear cell renal cell carcinoma. (2016)
  • Author(s): Mika Takahashi*, Tomoki Kai, Akinori Tokunaga, Takeo Nomura, Fuminori Sato, Keiko Matsuura, Masatsugu Moriyama, Hiromitsu Mimata,
  • Organizer: AUA2016 （アメリカ泌尿器科学会）
  • Place of Presentation: San Diego Convention Center (San Diego, CA)
  • Year and Date: 2016-05-06
• [Presentation] WDR20は淡明細胞型腎細胞癌の悪性化に関与する (2016)
  • Author(s): 高橋 美香, 松浦 恵子, 甲斐 友喜, 徳永 暁憲, 佐藤 文憲, 三股 浩光, 守山 正胤
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台国際センター、東北大学百周年記念会館（宮城県・仙台市）
  • Year and Date: 2016-04-23
• [Presentation] 腎特異的ノックアウトマウスモデルにおいて、SAV1 lossはHippo pathwayの抑制により腎尿細管上皮細胞に過剰増殖をもたらす (2016)
  • Author(s): 甲斐 友喜, 松浦 恵子, 塚本 善之, 高橋 美香, 中田 知里, 内田 智久, 泥谷 直樹, 佐藤 文憲, 守山 正胤, 三股 浩光
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台国際センター、東北大学百周年記念会館（宮城県・仙台市）
  • Year and Date: 2016-04-23
• [Presentation] WDR20は淡明型腎細胞癌の悪性化に関与する (2016)
  • Author(s): 高橋 美香, 松浦 恵子, 甲斐 友喜, 徳永 暁憲, 佐藤 文憲, 三股 浩光, 守山 正胤
  • Organizer: 第25回泌尿器科分子・細胞研究会
  • Place of Presentation: ハイアットリージェンシー大阪（大阪府大阪市）
  • Year and Date: 2016-02-26
• [Presentation] WDR20 is involved in the malignant transformation of clear cell renal cell carcinoma (ccRCC) (2015)
  • Author(s): Mika Takahashi*, Keiko Matsuura, Tomoki Kai, Akinori Tokunaga, Fuminori Sato, Hiromitsu Mimata, Masatsugu Moriyama
  • Organizer: 第67回西日本泌尿器科学会総会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2015-11-05
• [Presentation] 淡明細胞型腎細胞癌(ccRCC)の悪性化に関与する遺伝子の探索 (2015)
  • Author(s): 高橋 美香, 松浦 恵子, 甲斐 友喜, 徳永 暁憲, 佐藤 文憲, 三股 浩光, 守山 正胤
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 石川県立音楽堂（石川県金沢市）
  • Year and Date: 2015-04-18