Elucidation of the mechanism of Hippo pathway in RCC malignant transformation

• Project/Area Number: 24590415
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Oita University
• Principal Investigator: MATSUURA KEIKO 大分大学, 医学部, 准教授 (00291542)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 泌尿生殖器・内分泌 / 腎癌 / Hippoパスウェイ / SAV1

Outline of Final Research Achievements

SAV1, a component of the Hippo pathway, has been reported to be involved in malignant transformation of clear cell renal cell carcinoma (ccRCC). In this study, we found that re-expression of SAV1 inhibited RCC cell proliferation in vitro. In addition, immunohistochemistry frequently demonstrated nuclear localization of YAP1 in ccRCC cases with SAV1. Furthermore, tumors injected with SAV1 stable cell lines showed a decrease of tumor size and growth rate, compared with those of control. Pathway analysis revealed that TGFβ signaling was found to be inhibited in tumors with SAV1 stable cell lines. Based on these data, it is suggested that Hippo pathway including SAV1 acts as tumor suppressor, and downregulation of SAV1 is implicated in malignant formation in ccRCC through TGF beta signaling.

Research Products

• [Journal Article] Downregulation of NDUFB6 due to 9p24.1-p13.3 loss is implicated in metastatic clear cell renal cell carcinoma. (2015)
  • Author(s): Narimatsu T, *Matsuura K, Nakada C, Tsukamoto Y, Hijiya N, Kai T, Inoue T, Uchida T, Nomura T, Sato F, Seto M, Takeuchi I, Mimata H, Moriyama M
  • Journal Title: Cancer Medicine Volume: 4(1) Issue: 1 Pages: 112-124
  • DOI: 10.1002/cam4.351
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clear cell papillary renal cell carcinoma: a review. (2014)
  • Author(s): Kuroda N, Ohe C, Kawakami F, Mikami S, Furuya M, Matsuura K, Moriyama M, Nagashima Y, Zhow M, Petersson F, López JI, Hes O, Michal M, Amin MB.
  • Journal Title: Int J Clin Exp Pathol Volume: 7(11) Pages: 7312-7318
  • Peer Reviewed / Open Access
• [Journal Article] Molecular analysis of a case of renal cell carcinoma with t(6;11)(p21;q12) reveals a link to a lysosome-like structure. (2014)
  • Author(s): Matsuura K, Inoue T, Kai T, Yano S, Kashima K, Yokoyama S, Sato F, Nomura T, Mimata H, Moriyama M, Kuroda N, Nagashima Y
  • Journal Title: Histopathology Volume: 64 Issue: 2 Pages: 304-306
  • DOI: 10.1111/his.12238
  • Peer Reviewed
• [Journal Article] Chromophobe renal cell carcinoma with neuroendocrine differentiation/morphology: A clinicopathological and genetic study of three cases. (2014)
  • Author(s): Ohe C, Kuroda N, Matsuura K, Kai T, Moriyama M, Sugiguchi S, Terahata S, Hosaka N, Hes O, Michal M, Matsuda T, Uemura Y
  • Journal Title: Hum Pathol Volume: 1 Issue: 3 Pages: 31-39
  • DOI: 10.1016/j.ehpc.2014.08.003
  • Peer Reviewed / Open Access
• [Journal Article] The Vav3 oncogene enhances the malignant potential of prostate cancer cells under chronic hypoxia. (2014)
  • Author(s): Hirai K, Nomura T, Yamasaki M, Inoue T, Narimatsu T, Chisato Nakada PD, Yoshiyuki Tsukamoto PD, Matsuura K, Sato F, Moriyama M, Mimata H
  • Journal Title: Urol Oncol Volume: 32(2) Issue: 2 Pages: 101-109
  • DOI: 10.1016/j.urolonc.2012.09.005
  • Peer Reviewed
• [Journal Article] Targeting the Vav3 oncogene enhances docetaxel-induced apoptosis through the inhibition of androgen receptor phosphorylation in LNCaP prostate cancer cells under chronic hypoxia. (2013)
  • Author(s): Nomura T, Yamasaki M, Hirai K, Inoue T, Sato R, Matsuura K, Moriyama M, Sato F, Mimata H.
  • Journal Title: Mol Cancer. Volume: 12 Issue: 1 Pages: 27-27
  • DOI: 10.1186/1476-4598-12-27
  • Peer Reviewed
• [Journal Article] Genomic profiling of oral squamous cell carcinomaby array-based comparative genomic hybridization (2013)
  • Author(s): Yoshioka S, Tsukamoto Y, Hijiya N, Nakada C, Uchida T, Matsuura K, Takeuchi I, Seto M, Kawano K, Moriyama M
  • Journal Title: PLoS One Volume: 8(2) Issue: 2 Pages: 56165-56165
  • DOI: 10.1371/journal.pone.0056165
  • Peer Reviewed
• [Journal Article] Review of renal carcinoma with t(6;11)(p21;q12-13) with focus on clinical and pathobiological aspects. (2013)
  • Author(s): Kuroda N, Tanaka A, Sasaki N, Ishihara A, Matsuura K, Moriyama M, Nagashima Y, Inoue K, Petersson F, Martignoni G, Michal M, Hes O.
  • Journal Title: Histol Histopathol Volume: 28 Pages: 685-690
  • Peer Reviewed
• [Journal Article] MiR-29c is downregulated in gastric carcinomas and regulates cell proliferation by targeting RCC2. (2013)
  • Author(s): Matsuo M, Nakada C, Tsukamoto Y, Noguchi T, Uchida T, Hijiya N, Matsuura K, Moriyama M.
  • Journal Title: Mol Cancer Volume: 12(1) Pages: 15-15
  • Peer Reviewed
• [Presentation] ヒト腎細胞癌移植モデルマウスにおいてSAV1遺伝子は腫瘍増殖を抑制する (2014)
  • Author(s): 甲斐 友喜, 松浦 恵子, 中田千里、塚本 善之、泥谷 直樹、佐藤 文憲、小林 隆志、三股 浩光、守山 正胤, 三股 浩光
  • Organizer: 第73回日本癌学会
  • Place of Presentation: パシフィコ横浜, 横浜市
  • Year and Date: 2014-09-27
• [Presentation] 腎細胞癌移植モデルにおいてSAV1遺伝子は腫瘍増殖を抑制する (2014)
  • Author(s): 甲斐 友喜、松浦 恵子、泥谷 直樹、守山 正胤、三股 浩光
  • Organizer: 102回 日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場・神戸国際展示場・神戸ポートピアホテル, 神戸市
  • Year and Date: 2014-04-24
• [Presentation] ヒト腎細胞癌移植モデルマウスにおける癌抑制遺伝子候補SAV1遺伝子の抗腫瘍効果の検討
  • Author(s): 甲斐 友喜, 松浦 恵子, 泥谷 直樹, 守山 正胤, 三股 浩光
  • Organizer: 第101回 日本泌尿器科学会
  • Place of Presentation: 北海道札幌市
• [Presentation] 腎淡明細胞癌の転移に関わるゲノム異常の蓄積
  • Author(s): 成松 隆弘, 松浦 恵子, 泥谷 直樹, 中田 知里, 井上 享, 野村 威雄, 竹内 一郎, 瀬戸 加大, 佐藤 文憲, 守山 正胤, 三股 浩光
  • Organizer: 第101回 日本泌尿器科学会
  • Place of Presentation: 北海道札幌市
• [Presentation] Mutinous tubular and spindle cell carcinoma(MTSCC)の網羅的ゲノム異常解析
  • Author(s): 井上 享, 松浦 恵子, 長嶋 洋治, 野村 威雄, 佐藤 文憲, 守山 正胤, 三股 浩光
  • Organizer: 第101回 日本泌尿器科学会
  • Place of Presentation: 北海道札幌市
• [Presentation] ヒト腎細胞癌移植モデルマウスにおいてSAV1遺伝子は腫瘍増殖を抑制する
  • Author(s): 甲斐 友喜, 松浦 恵子, 泥谷 直樹 佐藤 文憲 守山 正胤, 三股 浩光
  • Organizer: 第23回泌尿器科分子・細胞研究会
  • Place of Presentation: 山形県山形市
• [Presentation] 腎細胞癌の悪性化に関わるHippoパスウェイの異常
  • Author(s): 松浦恵子, 中田知里, 成松隆弘, 塚本善之, 野村威雄, 佐藤文憲, 三股浩光, 瀬戸加大,守山正胤
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京都新宿区
• [Presentation] 網羅的ゲノム解析による腎癌転移関連遺伝子の同定と解析
  • Author(s): 成松隆弘, 松浦恵子, 泥谷直樹, 中田知里, 井上享, 野村威雄, 竹内一郎, 瀬戸加大, 佐藤文憲, 守山正胤, 三股浩光
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 神奈川県横浜市
• [Presentation] 集合管癌の網羅的ゲノム異常解析
  • Author(s): 井上享, 松浦恵子, 長嶋洋治, 成松隆弘, 野村威雄, 佐藤文憲, 守山正胤, 三股浩光
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: 神奈川県横浜市
• [Presentation] Identification of unique genomic profiles of collecting duct carcinoma
  • Author(s): Inoue T, Matsuura K, Nakata C, Nomura T, Sato F, Nagashima Y, Ohymama C, Habuchi T, Tomita Y, Takahashi S, Ogawa O, Nonomura N, Matsubara A, Nakagawa M, Moriyama M, Mimata H
  • Organizer: 2012 AUA Annual Meeting
  • Place of Presentation: Atlanta, USA
• [Book] 腫瘍病理鑑別診断アトラス 腎癌 (2013)
  • Author(s): 松浦 恵子, 守山 正胤 (長嶋洋二・黒田直人・松嵜 理 編集)
  • Publisher: 文光堂