Establishment of New Strategies for Treatment of Cancer Using TGF-beta Signaling

• Project/Area Number: 17016011
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: MIYAZONO Kohei The University of Tokyo, 大学院・医学系研究科, 教授 (90209908)
• Co-Investigator(Kenkyū-buntansha): MIYAZAWA Keiji 山梨大学, 大学院・医学工学総合研究部, 教授 (40209896) ; IMAMURA Takeshi (財)癌研究会, 癌研究所生化学部, 部長 (70264421) ; MAEDA Shingo (財)癌研究会, 癌研究所生化学部, 研究員 (60353463) ; WATABE Tetsuro 東京大学, 大学院・医学系研究科, 准教授 (00334235) ; SAITOH Masao 山梨大学, 大学院・医学系研究科, 准教授 (90345041) ; KANO Mitsunobu 東京大学, 大学院・医学系研究科, 講師 (80447383)
• Co-Investigator(Renkei-kenkyūsha): KOINUMA Daizo 東京大学, 大学院・医学系研究科, 講師 (80375071) ; EHATA Shogo 東京大学, 大学院・医学系研究科, 助教 (90506726)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥345,700,000 (Direct Cost: ¥345,700,000); Fiscal Year 2009: ¥69,100,000 (Direct Cost: ¥69,100,000); Fiscal Year 2008: ¥69,100,000 (Direct Cost: ¥69,100,000); Fiscal Year 2007: ¥69,100,000 (Direct Cost: ¥69,100,000); Fiscal Year 2006: ¥69,100,000 (Direct Cost: ¥69,100,000); Fiscal Year 2005: ¥69,300,000 (Direct Cost: ¥69,300,000)
• Keywords: TGF-β / 分子標的治療 / シグナル伝達 / がん幹細胞 / 転移 / 血管新生 / シグナル伝逹 / 胃がん / 脳腫瘍 / がん朝細胞 / 膵臓がん / 乳がん / DDS / Smad7

Research Abstract

TGF-βは強力な増殖抑制因子であるが、一方で上皮-間葉分化転換の促進などによりがんの浸潤・転移を促進する。本研究では、TGF-βシグナルの抑制が乳がんの転移を抑制し、脳腫瘍ではがん幹細胞の分化を促進することを示した。一方、スキルス胃がんではTGF-βは血管新生を抑制してがんの増殖を抑制することを見出した。またTGF-β拮抗剤とミセル型抗がん剤の併用は膵臓がんなどに有効であることを明らかにした。

Research Products

• [Journal Article] GF-βsignalling: a complex web in cancer progression (2010)
  • Author(s): Ikushima, H., Miyazono, K.
  • Journal Title: Nature Rev. Cancer 10(6) Pages: 415-424
• [Journal Article] Cellular context-dependent "colors" of transforming growth factor-βsignaling. (2010)
  • Author(s): Ikushima, H., Miyazono, K.
  • Journal Title: Cancer Sci. 101(2) Pages: 306-312
  • NAID: 10026587361
• [Journal Article] Context-dependent regulation of the expression of c-Ski protein by Arkadia in human cancer cells. (2010)
  • Author(s): Nagano, Y., Koinuma, D., Miyazawa, K., Miyazono, K.
  • Journal Title: J. Biochem. 147(4) Pages: 545-554
  • NAID: 10027875176
• [Journal Article] Bone morphogenetic protein receptors and signal transduction. (2010)
  • Author(s): Miyazono, K., Kamiya, Y., Morikawa, M.
  • Journal Title: J. Biochem. 147(1) Pages: 35-51
  • NAID: 10027873043
• [Journal Article] Bone morphogenetic protein receptors and signal transduction (2010)
  • Author(s): Miyazono, K., et al.
  • Journal Title: Journal of Biochemistry 147 Pages: 35-51
  • NAID: 10027873043
  • Peer Reviewed
• [Journal Article] Context-dependent regulation of the expression of c-Ski protein by Arkadia in human cancer cells (2010)
  • Author(s): Nagano, Y., et al.
  • Journal Title: Journal of Biochemistry 147 Pages: 545-554
  • Peer Reviewed
• [Journal Article] Cellular context-dependent "colors" of transforming growth factor-β signaling (2010)
  • Author(s): Ikushima, H., Miyazono, K.
  • Journal Title: Cancer Science 100 Pages: 306-312
  • NAID: 10026587361
  • Peer Reviewed
• [Journal Article] Forkhead box F1 regulates tumor-promoting properties of cancer-associated fibroblasts in lung cancer (2010)
  • Author(s): Saito, R.A., et al.
  • Journal Title: Cancer Research 70 Pages: 2644-2654
  • Peer Reviewed
• [Journal Article] Autocrine TGF-βsignaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMG-box factors. (2009)
  • Author(s): Ikushima, H., Todo, T., Ino, Y., Takahashi, M., Miyazawa, K., Miyazono, K.
  • Journal Title: Cell Stem Cell 5(5) Pages: 504-514
• [Journal Article] Promoter-wide analysis of Smad4 binding sites in human epithelial cells. (2009)
  • Author(s): Koinuma, D., Tsutsumi, S., Kamimura, N., Imamura, T., Aburatani, H., Miyazono, K.
  • Journal Title: Cancer Sci. 100(11) Pages: 2133-2142
  • NAID: 10027197070
• [Journal Article] Autophagy is activated by TGF-βand potentiates TGF- β-mediated growth inhibition in human hepatocellular carcinoma cells. (2009)
  • Author(s): Kiyono, K., Suzuki, H.I., Matsuyama, H., Morishita, Y., Komuro, A., Kano, M.R., Sugimoto, K., Miyazono, K.
  • Journal Title: Cancer Res. 69(23) Pages: 8844-8852
• [Journal Article] Thyroid transcription factor-1 inhibits transforming growth factor- β- mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells. (2009)
  • Author(s): Saito, R.A., Watabe, T., Horiguchi, K., Kohyama, T., Saitoh, M., Nagase, T., Miyazono, K.
  • Journal Title: Cancer Res. 69(7) Pages: 2783-2791
• [Journal Article] c-Ski overexpression promotes tumor growth and angiogenesis through inhibition of transforming growth factor-βsignaling in diffuse-type gastric carcinoma. (2009)
  • Author(s): Kiyono, K., Suzuki, H.I., Morishita, Y., Komuro, A., Iwata, C., Yashiro, M., Hirakawa, K., Kano, M.R., Miyazono, K.
  • Journal Title: Cancer Sci. 100(10) Pages: 1809-1816
  • NAID: 10027195355
• [Journal Article] Modulation of microRNA processing by p53. (2009)
  • Author(s): Suzuki, H.I., Yamagata, K., Sugimoto, K., Iwamoto, T., Kato, S., Miyazono, K.
  • Journal Title: Nature 460(7254) Pages: 529-533
• [Journal Article] Diffuse-type gastric carcinoma: Progression, angiogenesis, and transforming growth factor-βsignaling. (2009)
  • Author(s): Komuro, A., Yashiro, M., Iwata, C., Morishita, Y., Johansson, E., Matsumoto, Y., Watanabe, A., Aburatani, H., Miyoshi, H., Kiyono, K., Shirai, Y., Suzuki, H.I., Hirakawa, K., Kano, M.R., Miyazono, K.
  • Journal Title: J. Natl. Cancer Inst. 101(8) Pages: 592-604
• [Journal Article] SKI and MEL1 cooperate to inhibit transforming growth factor-βsignal in gastric cancer cells. (2009)
  • Author(s): Takahata, M., Inoue, Y., Tsuda, H., Imoto, I., Koinuma, D., Hayashi, M., Ichikura, T., Yamori, T., Nagasaki, K., Yoshida, M., Matsuoka, M., Morishita, K., Yuki, K., Hanyu, A., Miyazawa, K., Inazawa, J., Miyazono, K., Imamura T.
  • Journal Title: J. Biol. Chem. 284(5) Pages: 3334-3344
• [Journal Article] Comparison of the effects of the kinase inhibitors imatinib, sorafenib, and transforming growth factor-βreceptor inhibitor on extravasation of nanoparticles from neovasculature. (2009)
  • Author(s): Kano, M.R., Komuta, Y., Iwata, C., Oka, M., Shirai, Y., Morishita, Y., Ouchi, Y., Kataoka, K., Miyazono, K.
  • Journal Title: Cancer Sci. 100(1) Pages: 173-180
  • NAID: 10025141855
• [Journal Article] Chromatin immunoprecipitation on microarray analysis of Smad2/3 binding sites reveals roles of ETS1 and TFAP2A in transforming growth factorβsignaling. (2009)
  • Author(s): Koinuma, D., Tsutsumi, S., Kamimura, N., Taniguchi, H., Miyazawa, K., Sunamura, M., Imamura, T., Miyazono, K., Aburatani, H.
  • Journal Title: Mol. Cell. Biol. 29(1) Pages: 172-186
• [Journal Article] Role of Ras signaling in the induction of snail by transforming growth factor-β. (2009)
  • Author(s): Horiguchi, K., Shirakihara, T., Nakano, A., Imamura, T., Miyazono, K., Saitoh, M.
  • Journal Title: J. Biol. Chem. 284(1) Pages: 245-253
• [Journal Article] Thyroid transcription factor-1 inhibits transforming growth factor-β-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells (2009)
  • Author(s): Saito, R.A., et al.
  • Journal Title: Cancer Research 69 Pages: 2783-2791
  • Peer Reviewed
• [Journal Article] c-Ski overexpression promotes tumor growth and angiogenesis through inhibition of transforming growth factor-β signaling in diffuse-type gastric carcinoma (2009)
  • Author(s): Kiyono, K., et al.
  • Journal Title: Cancer Science 100 Pages: 1809-1816
  • Peer Reviewed
• [Journal Article] Modulation of microRNA processing by p53 (2009)
  • Author(s): Suzuki, H.I., et al.
  • Journal Title: Nature 460 Pages: 529-533
  • Peer Reviewed
• [Journal Article] Autocrine TGF-β signaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMG-box factors (2009)
  • Author(s): Ikushima, H., et al.
  • Journal Title: Cell Stem Cell 5 Pages: 504-514
  • Peer Reviewed
• [Journal Article] Promoter-wide analysis of Smad4 binding sites in human epithelial cells (2009)
  • Author(s): Koinuma, D., et al.
  • Journal Title: Cancer Science 100 Pages: 2133-2142
  • NAID: 10027197070
  • Peer Reviewed
• [Journal Article] Transforming growth factor-β signaling in epithelial-mesenchymal transition and progression of cancer (2009)
  • Author(s): Miyazono, K.
  • Journal Title: Proc Jpn Acad Ser B Phys Biol Sci. 85 Pages: 314-323
  • Peer Reviewed
• [Journal Article] Autophagy is activated by-TGF-β and potentiates TGF-β-mediated growth inhibition in human hepatocellular carcinoma cells (2009)
  • Author(s): Kiyono, K., et al.
  • Journal Title: Cancer Research 69 Pages: 8844-8852
  • Peer Reviewed
• [Journal Article] Polyplex micelles from triblock copolymers composed of tandemly aligned segments with biocompatible, endosomal escaping, and DNA-condensing functions for systemic gene delivery to pancreatic tumor tissue (2009)
  • Author(s): Miyata, K., et al.
  • Journal Title: Pharm Res. 25 Pages: 2924-2936
  • Peer Reviewed
• [Journal Article] Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo (2009)
  • Author(s): Yamamoto, M., et al.
  • Journal Title: J Cell Biol. 184 Pages: 323-334
  • Peer Reviewed
• [Journal Article] Comparison of the effects of the kinase inhibitors imatinib, sorafenib, and transforming growth factor-β receptor inhibitor on extravasation of nanoparticles from neovasculature (2009)
  • Author(s): Kano, M.R., et al.
  • Journal Title: Cancer Sci. 100 Pages: 173-180
  • Peer Reviewed
• [Journal Article] Chromatin immunoprecipitation on microarray analysis of Smad2/3 binding sites reveals roles of ETS1 and TFAP2A in transforming growth factor beta signaling (2009)
  • Author(s): Koinuma, D., et al.
  • Journal Title: Mol.Cell.Biol. 29 Pages: 172-186
  • Peer Reviewed
• [Journal Article] Crystallization and preliminary X-ray diffraction analysis of GCIP/HHM transcriptional regulator (2009)
  • Author(s): Seto, A., et al.
  • Journal Title: Acta Crystallogr Sect F Struct Biol Cryst Commun. 65 Pages: 21-24
  • Peer Reviewed
• [Journal Article] SKI and MEL1 cooperate to inhibit transforming growth factor-β signal in gastric cancer cells (2009)
  • Author(s): Takahata, M., et al.
  • Journal Title: J Biol Chem. 284 Pages: 3334-3344
  • Peer Reviewed
• [Journal Article] Role of Ras signaling in the induction of Snail by TGF-β (2009)
  • Author(s): Horiguchi, K., et al.
  • Journal Title: J Biol Chem. 284 Pages: 245-253
  • Peer Reviewed
• [Journal Article] Regulation of the stability of cell surface E-cadherin by the proteasome (2009)
  • Author(s): Saitoh, M., et al.
  • Journal Title: Biochem.Biophys.Res.Commun 381 Pages: 560-565
  • Peer Reviewed
• [Journal Article] Pin1 down-regulates transforming growth factor-β(TGF-β) signaling by inducing degradation of Smad proteins (2009)
  • Author(s): Nakano, A., et al.
  • Journal Title: J Biol Chem. 284 Pages: 6109-6115
  • Peer Reviewed
• [Journal Article] Diffuse-type gastric carcinoma : Progression, accelerated angiogenesis, and disruption of transforming growth factor-β signaling (2009)
  • Author(s): Komuro, A., et al.
  • Journal Title: J Natl Cancer Inst 101 Pages: 592-604
  • Peer Reviewed
• [Journal Article] Inhibition of endogenous TGF-βsignaling enhances lymphangiogenesis. (2008)
  • Author(s): Oka, M., Iwata, C., Suzuki, H.I., Kiyono, K., Morishita, Y., Watabe, T., Komuro, A., Kano, M.R., Miyazono, K.
  • Journal Title: Blood 111(9) Pages: 4571-4579
• [Journal Article] Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway. (2008)
  • Author(s): Katsuno, Y., Hanyu, A., Kanda, H., Ishikawa, Y., Akiyama, F., Iwase, T., Ogata, E., Ehata, S., Miyazono, K., Imamura, T.
  • Journal Title: Oncogene 27(49) Pages: 6322-6333
• [Journal Article] Snail is required for TGF- β-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells. (2008)
  • Author(s): Kokudo, T., Suzuki, Y., Yoshimatsu, Y., Yamazaki, T., Watabe, T., Miyazono, K.
  • Journal Title: J. Cell Sci. 121(20) Pages: 3317-3324
• [Journal Article] An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-βsignaling. (2008)
  • Author(s): Ikushima, H., Komuro, A., Isogaya, K., Shinozaki, M., Hellman, U., Miyazawa, K., Miyazono, K.
  • Journal Title: EMBO J. 27(22) Pages: 2955-2965
• [Journal Article] Specificity of the inhibitory effects of Dad on TGF-β family type I receptors, Thickveins, Saxophone, and Baboon in Drosophila (2008)
  • Author(s): Kamiya, Y., et al.
  • Journal Title: FEBS Lett. 582 Pages: 2496-2500
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein signaling enhances invasion and bone metastasis of breast cancer cells through Smad pathway (2008)
  • Author(s): Katsuno, Y., et al.
  • Journal Title: Oncogene 27 Pages: 6322-6333
  • Peer Reviewed
• [Journal Article] Shear activates platelet-derived latent TGF-beta (2008)
  • Author(s): Miyazono, K.
  • Journal Title: Blood 112 Pages: 3533-3534
• [Journal Article] SUMO amplifies TGF-beta signalling (2008)
  • Author(s): Miyazono, K., et al.
  • Journal Title: Nat Cell Biol. 10 Pages: 635-637
• [Journal Article] Snail is required for TGF-β-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells (2008)
  • Author(s): Kokudo, T., et al.
  • Journal Title: J Cell Sci. 121 Pages: 3317-3324
  • Peer Reviewed
• [Journal Article] An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signaling (2008)
  • Author(s): Ikushima, H., et al.
  • Journal Title: EMBO J. 27 Pages: 2955-2965
  • Peer Reviewed
• [Journal Article] BMPs promote proliferation and migration of endothelial cells via stimulation of VEGF-A/VEGFR2 and Angiopoietin-1/Tie2 signalling (2008)
  • Author(s): Suzuki, Y., et. al.
  • Journal Title: Journal of Biochemistry (Tokyo) 143 Pages: 199-206
  • Peer Reviewed
• [Journal Article] Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells (2008)
  • Author(s): Kawasaki, K., et. al.
  • Journal Title: Journal of Cell Biology (印刷中)
  • Peer Reviewed
• [Journal Article] Inhibition of endogenous TGF-β signaling enhances lymphangiogenesis (2008)
  • Author(s): Oka, M., et. al.
  • Journal Title: Blood (印刷中)
  • Peer Reviewed
• [Journal Article] Differential regulation of epithelial and mesenchymal markers byδEF1 proteins in epithelial mesenchymal transition induced by TGF-β. (2007)
  • Author(s): Shirakihara, T., Saitoh, M., Miyazono K.
  • Journal Title: Mol. Biol. Cell 18(9) Pages: 3533-3544
• [Journal Article] Selective inhibitory effects of Smad6 on bone morphogenetic protein type I receptors. (2007)
  • Author(s): Goto, K., Kamiya, Y., Imamura, T., Miyazono, K., Miyazawa, K.
  • Journal Title: J. Biol. Chem. 282(28) Pages: 20603-20611
• [Journal Article] Arkadia induces degradation of SnoN and c-Ski to enhance TGF-βsignaling. (2007)
  • Author(s): Nagano, Y., Mavrakis, K.J., Lee, K.L., Fujii, T., Koinuma, D., Sase, H., Yuki, K., Isogaya, K., Saitoh, M., Imamura, T., Episkopou, V., Miyazono, K., Miyazawa, K.
  • Journal Title: J. Biol. Chem. 282(28) Pages: 20492-20501
• [Journal Article] Transforming growth factor-βpromotes survival of mammary carcinoma cells through induction of anti-apoptotic transcription factor DEC1. (2007)
  • Author(s): Ehata, S., Hanyu, A., Hayashi, M., Aburatani, H., Kato, Y., Fujime, M., Saitoh, M., Miyazawa, K., Imamura, T., Miyazono, K.
  • Journal Title: Cancer Res. 67(20) Pages: 9694-9703
• [Journal Article] Modulation of the functional binding sites for TGF-βon the type II receptor leads to suppression of TGF-βsignaling. (2007)
  • Author(s): Shimanuki, T., Hara, T., Furuya, T., Imamura, T., Miyazono, K.
  • Journal Title: Oncogene 26(23) Pages: 3311-3320
• [Journal Article] Ki26894, a novel transforming growth factor-βtype I receptor kinase inhibitor, inhibits in vitro cell motility and invasion and in vivo bone metastasis of a human breast cancer cell line. (2007)
  • Author(s): Ehata, S., Hanyu, A., Katsuno, Y., Fukunaga, E., Goto, K., Ishikawa, Y., Nomura, K., Ogata, E., Fujime, M., Miyazono, K., Shimizu, K., Imamura, T.
  • Journal Title: Cancer Sci. 98(1) Pages: 127-133
• [Journal Article] Improvement of cancer-targeting therapy using nanocarriers for intractable solid tumors by inhibition of TGF-βsignalling. Proc. (2007)
  • Author(s): Kano, M.R., Bae, Y., Iwata, C., Morishita, Y., Yashiro, M., Oka, M., Fujii, T., Komuro, A., Kiyono, K., Kaminishi, M., Hirakawa, K., Ouchi, Y., Nishiyama, N., Kataoka, K., Miyazono, K.
  • Journal Title: Natl. Acad. Sci. USA 104(9) Pages: 3460-3465
• [Journal Article] Differentia1 regulation of epithelial and mesenchymal markers by δEFl proteins in epithelial mesenchymal transition induced by TCF-β (2007)
  • Author(s): Shirakihara, T., et. al.
  • Journal Title: Molecular Biology of the Cell 18 Pages: 3533-3544
  • Peer Reviewed
• [Journal Article] Transforming growth factor-β promotes survival of mammary carcino-ma cells through induction of anti-apoptotic transcription factor DEC1 (2007)
  • Author(s): Ehata, S., et. al.
  • Journal Title: Cancer Research 67 Pages: 9694-9703
  • Peer Reviewed
• [Journal Article] Arkadia induces degradation of SnoN and c-Ski to enhance TGF-βsignaling (2007)
  • Author(s): Nagano, Y., et. al.
  • Journal Title: Journal of Biological Chemistry 282 Pages: 20492-20501
  • Peer Reviewed
• [Journal Article] Selective inhibitory effects of Smad6 on bone morphogenetic protein type I receptors (2007)
  • Author(s): Goto, K., et. al.
  • Journal Title: Journal of Biological Chemistry 282 Pages: 20603-20611
  • Peer Reviewed
• [Journal Article] Modulation of the functional binding sites for TGF-β on type II receptor leads to suppression of TGF-β signaling (2007)
  • Author(s): Shimanuki, T., et. al.
  • Journal Title: Oncogene 26 Pages: 3311-3320
  • Peer Reviewed
• [Journal Article] Casein kinase 2-interacting protein-1, a novel Akt pleckstrin homology domain-interacting protein, down-regulates PI3K/Akt signaling and suppresses tumor growth in vivo (2007)
  • Author(s): Tokuda, E., et. al.
  • Journal Title: Cancer Research 67 Pages: 9666-9676
  • Peer Reviewed
• [Journal Article] Ki26894, a novel transforming growth factor-β type I receptor kinase inhibitor, inhibits in vitro cell motility and invasion and in vivo bone metastasis of a human breast cancer cell line. (2007)
  • Author(s): Ehata, S., et al.
  • Journal Title: Cancer Sci. 98 (1) Pages: 127-133
• [Journal Article] Activin/Nodal signaling is involved in propagation of mouse embryonic stem cells. (2007)
  • Author(s): Ogawa, K., et al.
  • Journal Title: J. Cell Sci. 120 (1) Pages: 55-65
• [Journal Article] Improvement of cancer-targeting therapy using nanocarriers for intractable solid tumors by inhibition of TGF-β signalling. (2007)
  • Author(s): Kano, M.R., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 (9) Pages: 3460-3465
• [Journal Article] Prox1 induces lymphatic endothelial differentiation via integrin α9 and other signaling cascades. (2007)
  • Author(s): Mishima, K., et al.
  • Journal Title: Mol. Biol. Cell 18 (4) Pages: 1421-1429
• [Journal Article] Modulation of the functional binding sites for TGF-β on the type II receptor leads to suppression of TGF-β signaling. (2007)
  • Author(s): Shimanuki, T., et al.
  • Journal Title: Oncogene (In press)
• [Journal Article] Execution of BMP-4- induced apoptosis by p53-dependent ER dysfunction in myeloma and B-cell hybridoma cells. (2006)
  • Author(s): Fukuda, N., Saitoh, M., Kobayashi, N., Miyazono, K.
  • Journal Title: Oncogene 25(25) Pages: 3509-3517
• [Journal Article] Nuclear and cytoplasmic c-Ski differentially modulate cellular functions. (2006)
  • Author(s): Nagata, M., Goto, K., Ehata, S., Kobayashi, N., Saitoh, M., Miyoshi, H., Imamura, T., Miyazawa, K., Miyazono, K.
  • Journal Title: Genes Cells 11(11) Pages: 1267-1280
• [Journal Article] Nuclear and cytoplasmic c-Ski differentially modulate cellular functions. (2006)
  • Author(s): Nagata, M., et al.
  • Journal Title: Genes Cells 11 (11) Pages: 1267-1280
• [Journal Article] BMP-4-induced apoptosis by p53-dependent ER dysfunction in myeloma and B-cell hybridoma cells (2006)
  • Author(s): Fukuda, N., et al.
  • Journal Title: Oncogene (In press)
• [Journal Article] VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B/PDGFRβsignaling. (2005)
  • Author(s): Kano, M.R., Morishita, Y., Iwata, C., Iwasaka, S., Watabe, T., Ouchi, Y., Miyazono, K., Miyazawa, K.
  • Journal Title: J. Cell Sci. 118(16) Pages: 3759-3768
• [Journal Article] The ALK-5 Inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-β. (2005)
  • Author(s): Tojo, M., Hamashima, Y., Hanyu, A., Kajimoto, T., Saitoh, M., Miyazono, K., Node, M., Imamura, T.
  • Journal Title: Cancer Sci. 96(11) Pages: 791-800
  • NAID: 10017091727
• [Journal Article] Effect of Smad7 expression on metastasis of mouse mammary carcinoma JygMC(A) cells. (2005)
  • Author(s): Azuma, H., Ehata, S., Miyazaki, H., Watabe, T., Maruyama, O., Imamura, T., Sakamoto, T., Kiyama, S., Kiyama, Y., Ubai, T., Inamoto, T., Takahara, S., Itoh, Y., Otsuki, Y., Katsuoka, Y., Miyazono, K., Horie, S.
  • Journal Title: J. Natl. Cancer Inst. 97(23) Pages: 1734-1746
• [Journal Article] Effect of Smad7 expression on metastasis of mouse mammary carcinoma JygMC(A) cells (2005)
  • Author(s): Azuma, H., et al.
  • Journal Title: J.Natl.Cancer Inst. 97・23 Pages: 1734-1746
• [Journal Article] VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B/PDGFRβ signaling (2005)
  • Author(s): Kano, M.R., et al.
  • Journal Title: J.Cell Sci. 118・16 Pages: 3759-3768
• [Journal Article] Degradation of the tumor suppressor Smad4 by WW and HECT-domain ubiquitin ligases (2005)
  • Author(s): Moren.A., et al.
  • Journal Title: J.Biol.Chem. 280・23 Pages: 22115-22123
• [Journal Article] BMP receptor signaling : transcriptional targets, regulation of signals, and signaling cross-talk (2005)
  • Author(s): Miyazono, K., et al.
  • Journal Title: Cytokine Growth Factor Rev. 16・3 Pages: 251-263
• [Journal Article] The ALK-5 Inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-β (2005)
  • Author(s): Tojo, M., et al.
  • Journal Title: Cancer Sci. 96・11 Pages: 791-800
• [Presentation] Roles of TGF-β signaling during endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells (2010)
  • Author(s): Watabe, T., et al.
  • Organizer: 8th Conference of AACR and JCA : Cancer Genomics, Epigenomics, and the Develop.of Novel Therapeutics
  • Place of Presentation: Hilton Waikoloa Village, Hawaii, USA
• [Presentation] TGF-b signaling in tumor microenvironment (2010)
  • Author(s): Miyazono, K.
  • Organizer: 8th Conference of AACR and JCA : Cancer Genomics, Epigenomics, and the Develop.of Novel Therapeutics
  • Place of Presentation: Hilton Waikoloa Village, Hawaii, USA
• [Presentation] Optimal choice of kinase inhibitors for manipulation of tumor vasculature : depending on the original degree of pericyte coverage (2009)
  • Author(s): Kano, M.R., et al.
  • Organizer: AACR 100th Annual Meeting 2009
  • Place of Presentation: Colorado Convention Center, Denver, USA
• [Presentation] TGF-β signaling in regulation of cancer-initiating cells and EMT (2009)
  • Author(s): Miyazono, K., et al.
  • Organizer: FASEB Summer Res.Conf.- TGF-β superfamily ; Signaling in Development and Disease
  • Place of Presentation: Carefree Resort, Arizona, USA
• [Presentation] Roles of signal and transcriptional networks during formation of lymphatic vessels(Symposium) (2009)
  • Author(s): Watabe, T.
  • Organizer: The 36th International Congress on Physiological Sciences
  • Place of Presentation: 京都・国立京都国際会館
• [Presentation] Function of Smad-Olig1 synexpression group (2009)
  • Author(s): Miyazawa, K.
  • Organizer: TGF-β meeting in Uppsala
  • Place of Presentation: University of Uppsala, Uppsala, Sweden
• [Presentation] Characterization of Smad binding sites by ChIP-chip (2009)
  • Author(s): Koinuma, D.
  • Organizer: TGF-β meeting in Uppsala
  • Place of Presentation: University of Uppsala, Uppsala, Sweden
• [Presentation] Snail is required for TGF-β-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells (2009)
  • Author(s): Watabe, T.
  • Organizer: TGF-β meeting in Uppsala
  • Place of Presentation: University of Uppsala, Uppsala, Sweden
• [Presentation] Optimal manipulation of tumor microvasculature for treatment of tumors using nanoparticles (2009)
  • Author(s): Miyazono, K.
  • Organizer: TGF-β meeting in Uppsala
  • Place of Presentation: University of Uppsala, Uppsala, Sweden
• [Presentation] Regulation of cancer stem cell differentiation by TGF-β signaling (2009)
  • Author(s): Miyazono, K.
  • Organizer: Japanese-German Cancer Workshop
  • Place of Presentation: Baurs Park, Hamburg, Germany
• [Presentation] Modulation of microRNA processing by p53 (2009)
  • Author(s): Suzuki, H.I.
  • Organizer: Japanese-German Cancer Workshop
  • Place of Presentation: Baurs Park, Hamburg, Germany
• [Presentation] Animal models for functional analysis of tumor vasculature (2009)
  • Author(s): Kano, M.R., et al.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ・横浜
• [Presentation] Autocrine TGF-β signaling maintains tumorigenicity of glioma-initiating cells (2009)
  • Author(s): Ikushima, H., et al.et al.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ・横浜
• [Presentation] Use of TGF-beta inhibitors for treatment of cancer (2009)
  • Author(s): Miyazono, K.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ・横浜
• [Presentation] Identification and characterization of diffuse-type gastric cancer-initiating cells (2009)
  • Author(s): Katsuno, Y., et al.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ・横浜
• [Presentation] Modulation of microRNA processing by p53 (2009)
  • Author(s): Suzuki, H.I., et al.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ・横浜
• [Presentation] Transcriptional networks of Prox1 and HoxD8 play important roles during lymphangiogenesis (2009)
  • Author(s): Watabe, T., et al.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ・横浜
• [Presentation] Regulation of microRNA processing by p53 (2009)
  • Author(s): Suzuki, H.I., et al.
  • Organizer: 第68回日本生化学会
  • Place of Presentation: 横浜パシフィコ・横浜
• [Presentation] Analysis of the interaction of Smad7 with TGF-β family type I receptors (2009)
  • Author(s): Kamiya, Y., et al.
  • Organizer: 第68回日本生化学会
  • Place of Presentation: 横浜パシフィコ・横浜
• [Presentation] Autocrine TGF-β signaling maintains tumorigenicity of glioma-initiating cells (2009)
  • Author(s): Ikushima, H., et al.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜パシフィコ・横浜
• [Presentation] Snail is required for TGF-β-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells (2009)
  • Author(s): Watabe, T., et al.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜パシフィコ・横浜
• [Presentation] Clinicopathological analysis for glioma-specific vascular structures (2009)
  • Author(s): Nishihara, H., Kano, M.R., et al.
  • Organizer: AACR Special Conference, Genetics and Biology of Brain Cancers
  • Place of Presentation: Omni San Diego Hotel San Diego, CA, USA
• [Presentation] TGF-β signaling and Cancer (2008)
  • Author(s): Miyazono K
  • Organizer: Uppsala University, Rudbeck seminar
  • Place of Presentation: Uppsala, Sweden(ウプサラ大学)
  • Year and Date: 2008-10-23
• [Presentation] TGF-β Signaling and Cancer (2008)
  • Author(s): Miyazono K
  • Organizer: Anita Roberts Symposium : TGF-β : Discovery and Promise
  • Place of Presentation: Bethesda, USA (NIH ; National Institute of Health)
  • Year and Date: 2008-09-19
• [Presentation] Regulation of angiogenesis and lymphangiogenesis by TGF-β signaling (2008)
  • Author(s): Miyazono, K., et. al.
  • Organizer: The U.S. Japan Cooperative Cancer Research Program Workshop
  • Place of Presentation: 京都
  • Year and Date: 2008-03-19
• [Presentation] Deletion of TGF-β signaling in diffuse-type gastric cancer cells promotes tumor progression in vivo via alteration of tumor microenvironment (2008)
  • Author(s): Komuro, A., et. al.
  • Organizer: Keystone Symposium "TGF-β Family in Homeostasis and Disease"
  • Place of Presentation: Arizona, USA
  • Year and Date: 2008-02-05
• [Presentation] TGF-β signaling and cancer (2008)
  • Author(s): Miyazono K
  • Organizer: EMBO meeting on Cellular Signaling & Molecular Medicine 2008
  • Place of Presentation: Cavtat/Dubrovnik, Croatia (Hotel Croatia)
• [Presentation] スキルス胃癌の増殖・進展におけるTGF-βの役割 (2008)
  • Author(s): 古室暁義, 他
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢市(石川県立音楽堂、他)
• [Presentation] An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signaling (2008)
  • Author(s): Ikushima H, et al.
  • Organizer: The 28th Sapporo Cancer Seminar International Symposium "TGF-β signaling and cancer"
  • Place of Presentation: 札幌市(北海道大学学術交流会館)
• [Presentation] Snail is required for TGF-β-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells (2008)
  • Author(s): Watabe T, et al.
  • Organizer: The 28th Sapporo Cancer Seminar International Symposium "TGF-β signaling and cancer"
  • Place of Presentation: 札幌市(北海道大学学術交流会館)
• [Presentation] Deletion of TGF-β signaling in diffuse-type gastric cancer cells promotes tumor progression in vivo via alteration of tumor microenvironment (2008)
  • Author(s): Komuro A, et al.
  • Organizer: The 28th Sapporo Cancer Seminar International Symposium "TGF-β signaling and cancer"
  • Place of Presentation: 札幌市(北海道大学学術交流会館)
• [Presentation] Involvement of Ras signaling in Snail transcription induced by TGF-β (2008)
  • Author(s): Horiguchi K, et al.
  • Organizer: The 28th Sapporo Cancer Seminar International Symposium "TGF-β signaling and cancer"
  • Place of Presentation: 札幌市(北海道大学学術交流会館)
• [Presentation] An Id-like molecule, Maid, is a syn-expression group-restricted regulator of TGF-β signaling (2008)
  • Author(s): Miyazawa K, et al.
  • Organizer: TGF-β Meeting in Leiden
  • Place of Presentation: Leiden, Netherlands(ライデン大学医学センター)
• [Presentation] TGF-β promotes survival of mammary carcinoma cells through induction of antiapoptotic transcription factor DEC1 (2008)
  • Author(s): Ehata S, et al.
  • Organizer: TGF-β Meeting in Leiden
  • Place of Presentation: Leiden, Netherlands(ライデン大学医学センター)
• [Presentation] Optimal manipulation of tumor vasculature for treatment of intractable solid tumors using nanoparticles (2008)
  • Author(s): Kano, MR.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋市(名古屋国際会議場)
• [Presentation] Enhancement of TGF-β signaling by Arkadia-induced degradation of c-Ski and SnoN (2008)
  • Author(s): Nagano Y, et al.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋市(名古屋国際会議場)
• [Presentation] New horizon of cancer research : from basic to translational research (2008)
  • Author(s): Miyazono K
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋市(名古屋国際会議場)
• [Presentation] Clinical Application of Nanoparticles on Cancer Therapy (2008)
  • Author(s): Miyazono K
  • Organizer: Micro- and Nano-Technologies in Medicine : A Swedish-Japanese Collaborative Workshop
  • Place of Presentation: Uppsala, Sweden(ウプサラ大学)
• [Presentation] AP2μはE3リガーゼArkadiaによりLys27リンクのユビキチン化が促進される (2008)
  • Author(s): 水谷アンナ, 他
  • Organizer: 日本分子生物学会生化学会合同大会BMB 2008
  • Place of Presentation: 神戸市(神戸ポートアイランド)
• [Presentation] TGF-β誘導性EMTへのFGFシグナルの関与 (2008)
  • Author(s): 白木原琢哉, 他
  • Organizer: 日本分子生物学会生化学会合同大会BMB 2008
  • Place of Presentation: 神戸市(神戸ポートアイランド)
• [Presentation] TGF-β signaling in fibrosis, angiogenesis, and lymphangiogenesis (2007)
  • Author(s): Miyazono, K., et. al.
  • Organizer: FASEB Summer Research Conference: TGF-β Superfamily: Signaling & Development
  • Place of Presentation: Arizona, USA
  • Year and Date: 2007-07-18
• [Presentation] TGFβ阻害剤とナノキャリアの併用による難治固形がん治療 (2007)
  • Author(s): 狩野光伸, 他.
  • Organizer: 第23回日本DDS学会
  • Place of Presentation: 熊本
  • Year and Date: 2007-06-15
• [Presentation] Selective inhibitory effects of Smad6 on bone morphogenetic protein type I receptors (2007)
  • Author(s): Miyazawa, K., et. al.
  • Organizer: TGF-β Meeting in Uppsala
  • Place of Presentation: Uppsala, Sweden
  • Year and Date: 2007-05-23
• [Presentation] A potential role of Arkadia on clathrin-dependent endocytosis (2007)
  • Author(s): Mizutani, A., et. al.
  • Organizer: TGF-β Meeting in Uppsala
  • Place of Presentation: Uppsala, Sweden
  • Year and Date: 2007-05-23
• [Presentation] An Id-like protein, Mai/DIP1, as a novel regulator of TGF-β signaling (2007)
  • Author(s): Ikushima, H., et. al.
  • Organizer: TGF-β Meeting in Uppsala
  • Place of Presentation: Uppsala, Sweden
  • Year and Date: 2007-05-23
• [Presentation] TGF-βシグナルによるがんの進展とその制御 (2007)
  • Author(s): 宮園 浩平
  • Organizer: 第27回日本医学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2007-04-06
• [Book] The TGF-βFamily. (2008)
  • Author(s): Derynck, R., Miyazono, K., eds.
  • Publisher: Cold Spring Harbor Laboratory Press
• [Book] The TGF-β Family (2008)
  • Author(s): Derynck, R. and Miyazono, K.
  • Total Pages: 1093
  • Publisher: Cold Spring Harbor Laboratory Press
• [Remarks]
  • URL: http://beta-lab.umin.ac.jp/
• [Remarks]
  • URL: http://beta-lab.umin.ac.jp/
• [Remarks]
  • URL: http://beta-lab.umin.ac.jp/
• [Remarks]
  • URL: http://beta-lab.umin.ac.jp/
• [Patent(Industrial Property Rights)] グリオーマ幹細胞の分化促進剤 (2010)
  • Inventor(s): 宮園浩平、生島弘彬、宮澤恵二, 他
  • Industrial Property Rights Holder: 東京大学
  • Filing Date: 2010-02-10
• [Patent(Industrial Property Rights)] グリオーマ幹細胞の分化促進剤 (2010)
  • Inventor(s): 宮園浩平, 他
  • Industrial Property Rights Holder: 東京大学
  • Filing Date: 2010-02-10
  • Overseas
• [Patent(Industrial Property Rights)] TGF-βシグナル阻害剤と抗腫瘍剤の組合せ使用 (2006)
  • Inventor(s): 宮園浩平、片岡一則、狩野光伸、べーユンスー、西山伸宏、平川弘聖、八代正和、野出學
  • Industrial Property Rights Holder: 東京大学
  • Acquisition Date: 2006-02-01
• [Patent(Industrial Property Rights)] TGF-βシダナル阻害剤と抗腫瘍剤の組み合せ使用 (2006)
  • Inventor(s): 宮園浩平他7名
  • Industrial Property Rights Holder: 科学技術振興機構
  • Industrial Property Number: 2006-024843
  • Filing Date: 2006-02-01