Molecular basis of Src-induced tumorigenesis

• Project/Area Number: 22689009
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Osaka University
• Principal Investigator: ONEYAMA Chitose 大阪大学, 微生物病研究所, 准教授 (90373208)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000); Fiscal Year 2011: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2010: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
• Keywords: 分子腫瘍学 / Src / ラフト / マイクロRNA

Research Abstract

In c-Src-induced transformation, we found that the lipid composition of rafts and the expression of lipid metabolism genes are changed. The addition of cholesterol to rafts efficiently suppressed c-Src-induced cell transformation. We also found that the miR-99a-mTOR/ FGFR3 pathway is crucial for controlling tumor growth and that c-Src. miR-542-3p. ILK. FAK circuit plays a pivotal role in controlling tumor progression. Our study provides insights into these novel signaling axes in the Src-related oncogenic pathway.

Research Products

• [Journal Article] MicroRNA-mediated upregulation of integrin-linked kinase promotes Src-induced tumor progression (2012)
  • Author(s): Oneyama C, Morii E, Okuzaki D, Takahashi Y, Ikeda J, Wakabayashi N, Akamatsu H, Tsujimoto M, Nishida T, Aozasa K, Okada M
  • Journal Title: Oncogene 2012 Volume: 31(13) Issue: 13 Pages: 1623-35
  • DOI: 10.1038/onc.2011.367
  • Peer Reviewed
• [Journal Article] The late endosome/ lysosome-anchored p18-mTORC1 pathway controls terminal maturation of lysosomes (2012)
  • Author(s): Takahashi Y, Nada S, Mori S, Soma-Nagae T, Oneyama C, Okada M
  • Journal Title: Biochem Biophys Res Commun Volume: 417(4) Pages: 1151-7
  • Peer Reviewed
• [Journal Article] Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase(MMP-13) expression (2012)
  • Author(s): Yamagata K, Li X, Ikegaki S, Oneyama C, Okada M, Nishita M, Minami Y
  • Journal Title: J Biol Chem Volume: 287(2) Issue: 2 Pages: 1588-99
  • DOI: 10.1074/jbc.m111.315127
  • Peer Reviewed
• [Journal Article] The late endosome/lysosome-anchored p18-mTORC1 pathway controls terminal maturation of lysosomes (2012)
  • Author(s): Takahashi Y, Nada S, Mori S, Soma-Nagae T, Oneyama C, Okada M
  • Journal Title: Biochem Biophys Res Commun Volume: 417(4) Issue: 4 Pages: 1151-7
  • DOI: 10.1016/j.bbrc.2011.12.082
  • Peer Reviewed
• [Journal Article] MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways (2011)
  • Author(s): Oneyama C, Ikeda J, Okuzaki D, Suzuki K, Kanou T, Shintani Y, Morii E, Okumura M, Aozasa K, Okada M
  • Journal Title: Oncogene 2011 Volume: 30(32) Issue: 32 Pages: 3489-501
  • DOI: 10.1038/onc.2011.63
  • Peer Reviewed
• [Journal Article] The guanine nucleotide exchange factor Arhgef5 plays crucial roles in Src-induced podosome formation (2011)
  • Author(s): Kuroiwa, Oneyama C, Nada S, Okada M
  • Journal Title: J Cell Sci 2011 Volume: 124(Pt 10) Issue: 10 Pages: 1726-38
  • DOI: 10.1242/jcs.080291
  • Peer Reviewed
• [Journal Article] Down-regulation of the tumor suppressor Cbp/PAG1 is mediated by epigenetic histone modifications via the MAPK/ PI3K pathway (2011)
  • Author(s): Suzuki K, Oneyama C, Kimura H, Tajima S, Okada M
  • Journal Title: J Biol Chem 2011 Volume: 286(18) Issue: 18 Pages: 15698-706
  • DOI: 10.1074/jbc.m110.195362
  • Peer Reviewed
• [Journal Article] The transmembrane adaptor Cbp/PAG1 controls the malignant potential of human non-small cell lung cancers that have c-src upregulation (2011)
  • Author(s): Kanou T, Oneyama C, Kawahara K, Okimura A, Ohta M, Ikeda N, Shintani Y, Okumura M, Okada M
  • Journal Title: Mol Cancer Res Volume: 9(1) Issue: 1 Pages: 103-14
  • DOI: 10.1158/1541-7786.mcr-10-0340
  • Peer Reviewed
• [Journal Article] Micro RNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways. (2011)
  • Author(s): Oneyama Chitose
  • Journal Title: Oncogene Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] A guanine nucleotide exchange factor Arhgef5 plays crucial roles in c-Src-induced podosome formation. (2011)
  • Author(s): Miho Kuroiwa
  • Journal Title: J Cell Sci Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Downregulation of the tumor suppressor Cbp/PAG1 is mediated by epigenetic histone modifications via the MAPK/PI3K pathway. (2011)
  • Author(s): Kei Suzuki
  • Journal Title: J Biol Chem. Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] The transmembrane adaptor Cbp/PAG1 controls the malignant potential of human non-small cell lung cancers that have c-src upregulation. (2011)
  • Author(s): Takashi Kanou
  • Journal Title: Mol Cancer Res. Volume: 9 Pages: 103-114
  • Peer Reviewed
• [Journal Article] a CDK inhibitor, effectively suppresses Src-mdiated transformation by inhibiting both CDKs and c-Src (2010)
  • Author(s): Hikita T, Oneyama C, Okada M. Purvalanol A
  • Journal Title: Genes Cells Volume: 15(10) Issue: 10 Pages: 1051-1062
  • DOI: 10.1111/j.1365-2443.2010.01439.x
  • Peer Reviewed
• [Journal Article] Exendin-4 suppresses SRC activity and reactive oxygen species production in diabetic Goto-Kakizaki rat islets in an Epac-dependent manner (2010)
  • Author(s): Mukai E, Fujimoto S, Sato H, Oneyama C, Kominato R, Sato Y, Sasaki M, Nishi Y, Okada M, Inagaki N
  • Journal Title: Diabetes Volume: 60(1) Issue: 1 Pages: 218-226
  • DOI: 10.2337/db10-0021
  • Peer Reviewed
• [Journal Article] Exendin-4 suppresses SRC activation and reactive oxygen species production in diabetic Goto-Kakizaki rat islets in an Epac-dependent manner. (2010)
  • Author(s): Mukai Eri
  • Journal Title: Diabetes Volume: 60 Pages: 218-226
  • Peer Reviewed
• [Journal Article] Purvalanol A, a CDK inhibitor, effectively suppresses Src-mediated transformation by inhibiting both CDKs and c-Src. (2010)
  • Author(s): Tomoya Hikita
  • Journal Title: Genes Cells Volume: 15 Pages: 1051-1062
  • Peer Reviewed
• [Presentation] スフィンゴミエリン分解酵素nSMase2によるがん形質発現制御機構の解析 (2011)
  • Author(s): 安藤雄哉、梶原健太郎、小根山千歳、岡田雅人
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] microRNAによるSrcがん化抑制機構の解析 (2011)
  • Author(s): 鬼頭頼子、岡田雅人、小根山千歳
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] microRNAによるSrcがん悪性化の制御機構の解析 (2011)
  • Author(s): 若林菜穂子、森井英一、奥崎大介、高橋佑介、池田純一郎、岡田雅人、小根山千歳
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] Metabolic alteration of lipid components in membrane microdomain by c-Src-induced transformation (2011)
  • Author(s): 梶原健太郎、小根山千歳、今本文男、岡田雅人
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Srcによるがん形質発現メカニズムの再考-マイクロRNAを介したシグナル制御 (2011)
  • Author(s): 小根山千歳
  • Organizer: 北海道大学大学院医学研究科
  • Place of Presentation: 札幌
  • Year and Date: 2011-11-04
• [Presentation] Srcによるがん形質発現メカニズムの再考-マイクロRNAを介したシグナル制御 (2011)
  • Author(s): 小根山千歳
  • Organizer: 北海道大学大学院医学研究科セミナー
  • Place of Presentation: 北海道(招待講演)
  • Year and Date: 2011-11-04
• [Presentation] がん細胞正常化を目指して.細胞内シグナルのリチューニング (2011)
  • Author(s): 小根山千歳
  • Organizer: 大分統計談話会
  • Place of Presentation: 大分
  • Year and Date: 2011-10-13
• [Presentation] 「がん細胞正常化」を目指して-細胞内シグナルのリチューニング (2011)
  • Author(s): 小根山千歳
  • Organizer: 大分統計談話会特別講演
  • Place of Presentation: 大分(招待講演)
  • Year and Date: 2011-10-13
• [Presentation] MicroRNA controls c-Src-induced tumor progression (2011)
  • Author(s): 小根山千歳、森井英一、奥崎大介、高橋佑介、若林菜穂子、池田純一郎、青笹克之、岡田雅人
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] miRNAによるSrcがん悪性化の制御機構 (2011)
  • Author(s): 小根山千歳、若林菜穂子、森井英一、奥崎大介、高橋佑介、池田純一郎、鬼頭頼子、浅井麗伊、岡田雅人
  • Organizer: 第3回日本RNAi研究会
  • Place of Presentation: 広島
  • Year and Date: 2011-08-26
• [Presentation] miRNAによるSrcがん悪性化の制御機構 (2011)
  • Author(s): 小根山千歳
  • Organizer: 第3回RNAi研究会
  • Place of Presentation: 広島
  • Year and Date: 2011-08-26
• [Presentation] マイクロRNAによるSrcがん形質発現の制御機構 (2011)
  • Author(s): 小根山千歳
  • Organizer: 岡山大学大学院医歯薬学総合研究科
  • Place of Presentation: 岡山
  • Year and Date: 2011-07-15
• [Presentation] Srcによるがん形質発現メカニズムの再考 (2011)
  • Author(s): 小根山千歳
  • Organizer: 岡山大学大学院医歯薬学総合研究科特別セミナー
  • Place of Presentation: 岡山(招待講演)
  • Year and Date: 2011-07-15
• [Presentation] miRNAによるSrcがん形質発現の抑制機構 (2010)
  • Author(s): 小根山千歳、鈴木慶、池田純一郎、狩野孝、奥崎大介、鬼頭頼子、若林菜穂子、森井英一、青笹克之、岡田雅人
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] MicroRNA involvement in c-Src-induced transformation (2010)
  • Author(s): 小根山千歳
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] MicroRNA involvement c-Src-induced transformation (2010)
  • Author(s): 小根山千歳、池田純一郎、鈴木慶、狩野孝、奥崎大介、森井英一、野島博、青笹克之、岡田雅人
  • 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] Srcによるがん形質発現のmiRNAによる調節機構 (2010)
  • Author(s): 小根山千歳
  • Organizer: 第2回RNAi研究会
  • Place of Presentation: 広島
  • Year and Date: 2010-08-29
• [Presentation] Srcによるがん形質発現のmiRNAによる調節機構 (2010)
  • Author(s): 小根山千歳、鈴木慶、池田純一郎、狩野孝、奥崎大介、森井英一、青笹克之、岡田雅人
  • Organizer: 第2回日本RNAi研究会
  • Place of Presentation: 広島
  • Year and Date: 2010-08-28
• [Presentation] Regulation of oncogenic potential of Src family kinases via membrane microdomain (2010)
  • Author(s): 小根山千歳、飯野琢也、疋田智也、岡田雅人
  • Organizer: 第27回内藤コンファレンス
  • Place of Presentation: 札幌
  • Year and Date: 2010-06-30
• [Presentation] Regulation of oncogenic potential of Src family kinases via membrane microdomain (2010)
  • Author(s): 小根山千歳
  • Organizer: 第27回内藤コンファレンス
  • Place of Presentation: 北海道
  • Year and Date: 2010-06-30
• [Presentation] Srcによるがん形質発現メカニズム (2010)
  • Author(s): 小根山千歳
  • Organizer: 第12回守田科学研究奨励賞受賞記念講演
  • Place of Presentation: 東京大学女性協会
  • Year and Date: 2010-06-05
• [Presentation] Srcによるがん形質発現メカニズムの再考 (2010)
  • Author(s): 小根山千歳、岡田雅人
  • Organizer: 第2回シグナルネットワーク研究会
  • Place of Presentation: 大阪
  • Year and Date: 2010-05-21
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/biken/oncogene/index.htm
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/biken/oncogene/index.htm
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/biken/oncogene/index.htm
• [Patent(Industrial Property Rights)] mTOR阻害剤の投与が有効ながん患者の選択方法 (2011)
  • Inventor(s): 小根山千歳、岡田雅人、田村研治
  • Industrial Property Rights Holder: 大阪大学
  • Industrial Property Number: 2011-218271
  • Filing Date: 2011-09-30
• [Patent(Industrial Property Rights)] mTOR阻害剤の投与が有効ながん患者の選択方法 (2011)
  • Inventor(s): 小根山千歳
  • Industrial Property Rights Holder: 大阪大学
  • Industrial Property Number: 2011-218271
  • Filing Date: 2011-09-30