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Department of Biochemistry
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Research Projects
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Our research covers signal transduction and molecular mechanisms of tumor progression.
Especially we focus on the roles of transforming growth factor-β (TGF-β) and transcription
factors that induce malignant phenotypes of cancer cells, i.e. δEF1 (ZEB1) and SIP1 (ZEB2).
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1.TGF-β signaling and tumor progression
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TGF-β is a growth factor that is widely distributed in our body, and most cells are thought to express signaling receptors for TGF-β.
Intriguingly, TGF-β evokes distinct cellular responses in different types of target cell,
which may be beneficial or detrimental depending on the contexts of its action. For example,
TGF-β is a tumor suppressor in normal cells, while it facilitates malignant phenotypes in transformed cells.
We try to elucidate the molecular basis underlying the context-dependent TGF-β signaling.
Our research will lead to development of strategies to regulate TGF-β signaling in a cell-response-selective manner.
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＜Selected Publications> |
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| Saitoh M, Endo K, Furuya S, Minami M, Fukasawa A, Imamura T, Miyazawa K STAT3 integrates cooperative Ras and TGF-β signals that induce Snail expression. Oncogene. 2016 Feb 25;35(8):1049-57 |
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| Motizuki M, Isogaya K, Miyake K, Ikushima H, Kubota T, Miyazono K, Saitoh M, Miyazawa K. Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β. J Biol Chem. 288:18911-18922 (2013) |
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| Ikushima H, Komuro A, Isogaya K, Shinozaki M, Hellman U, Miyazawa K, Miyazono K. An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-β signalling. EMBO J. 27:2955-2965 (2008) |
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2. Regulators of malignant phenotypes of cancer cells
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Malignant phenotypes of cancer cells are regulated by a plethora of factors.
Among those, we focus on transcription factors, δEF1 (ZEB1) and SIP1 (ZEB2),
as well as RNA splicing factors ESRP1/2 (epithelial splicing regulatory proteins).
We recently found that these factors form a complex network to regulate malignant phenotypes of cancer cells,
through mutually affecting expression and functions.
We aim to find strategies to suppress tumor progression by manipulating this complex network.
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＜Selected Publications> |
| Ishii H, Saitoh M, Sakamoto K, Kondo T, Katoh R, Tanaka S, Motizuki M, Masuyama K, Miyazawa K. Epithelial Splicing Regulatory Proteins 1 (ESRP1) and 2 (ESRP2) Suppress Cancer Cell Motility via Different Mechanisms. J Biol Chem. 2014 Oct 3;289(40):27386-99. |
| Horiguchi K, Sakamoto K, Koinuma D, Semba K, Inoue A, Inoue S, Fujii H, Yamaguchi A, Miyazawa K, Miyazono K, Saitoh M. TGF-β drives epithelial-mesenchymal transition through δEF1-mediated downregulation of ESRP. Oncogene. 2012 Jun 28;31(26):3190-201. |
| Shirakihara T, Horiguchi K, Miyazawa K, Ehata S, Shibata T, Morita I, Miyazono K, Saitoh M. TGF-beta regulates FGF receptor isoform switching and epithelial-mesenchymal transition. EMBO J. 2011 Feb 16;30(4):783-95. |
| Members | |
| Keiji Miyazawa | Professor |
| Masao Saitoh | Professor (Center for Medical Education and Sciences) |
| Shigeo Otake | Research Associate |
| Yuka Itoh | Research Associate |
| Takashi Yokoyama | Research Associate |
| Arisa Kinouchi | PhD student (Otolaryngology) |
| Fu Hao | PhD student (Medicine) |
| Asuka Obikane | MSc Student |
| Kaori Endo | Technical Staff |
| Chiho Omata | Technical Staff |
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Link to
Publications list
Department of Biochemistry,Faculty of Medicine, Universtiy of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898 JAPAN 
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