Department of Biochemistry

Research Projects
°°Our research covers signal transduction and molecular mechanisms of tumor progression. Especially we focus on the roles of transforming growth factor-¶¬ (TGF-¶¬) and transcription factors that induce malignant phenotypes of cancer cells, i.e. ¶ńEF1 (ZEB1) and SIP1 (ZEB2).

1.TGF-¶¬ signaling and tumor progression
°°TGF-¶¬ is a growth factor that is widely distributed in our body, and most cells are thought to express signaling receptors for TGF-¶¬. Intriguingly, TGF-¶¬ 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-¶¬ 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-¶¬ signaling. Our research will lead to development of strategies to regulate TGF-¶¬ signaling in a cell-response-selective manner.

°„Selected Publications>
Saitoh M, Endo K, Furuya S, Minami M, Fukasawa A, Imamura T, Miyazawa K
STAT3 integrates cooperative Ras and TGF-¶¬ signals that induce Snail expression.

Oncogene. 2016 Feb 25;35(8):1049-57

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-¶¬.

J Biol Chem. 288:18911-18922 (2013)

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-¶¬ signalling.
EMBO J. 27:2955-2965 (2008)

2. Regulators of malignant phenotypes of cancer cells
°°Malignant phenotypes of cancer cells are regulated by a plethora of factors. Among those, we focus on transcription factors, ¶ńEF1 (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.

°„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-¶¬ drives epithelial-mesenchymal transition through ¶ńEF1-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.

Keiji Miyazawa Professor
Masao Saitoh Professor°°(Center for Medical Education and Sciences)
Mitsuyoshi Motizuki Senior Research Associate
Yuka Itoh Research Associate
Shigeo Otake Research Associate
Takashi Yokoyama Research Associate
Yujiro Kimura PhD student (Department of Dentistry & Oral Surgery)
Mai Koizumi PhD student (Department of Dentistry & Oral Surgery)
Fu Hao MSc Student
Jinya Kumazawa Medical Student
Kaori Endo Technical Staff
Chiho Omata Technical Staff
Minori Kichiraku Secretary

Link to Publications list

Department of Biochemistry,Faculty of Medicine, Universtiy of Yamanashi,
1110 Shimokato, Chuo, Yamanashi, 409-3898 JAPAN °°Mail