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 - Basic Medicine (Core Departments) - Molecular Biology
Molecular Oncology
Cancer originates from a small number of normal cells (often a single cell) in the body that progressively acquire un-controllable, proliferative potentials and eventually form tumors. Cancer is sometimes called “disease of the cell” or “disease of genes”, since cancer-derived cells have some properties distinguishable from those of normal counterparts and since these special properties can be attributed to genetic alterations or mutations. Molecular Oncology is the research field where scientists try to discover molecules (and their alterations) underlying the malignant behaviors of cancer cells, to elucidate their functions, and to utilize the knowledge and materials obtained from such studies in developing effective methods of cancer therapy. The main focus of our research group is to find and characterize molecules that play important roles in the malignant behaviors of cancer cells such as recruitment of capillary blood vessels (or angiogenesis), invasion, and metastasis.

  Makoto Noda, Ph.D.
Professor
Research and Education
It has been know for more than 30 years that cell hybrids between normal cells and cancer cells show non-malignant phenotype. It was also found that the DNA extracted from cancer cells can confer malignant phenotype when introduced into normal cells. These apparently conflicting findings are considered today to indicate the presence of multiple types of mutations in cancer cells: i.e., inactivation of tumor suppressor genes and activation of cancer-causing genes (or oncogenes).
Through screening the genes with ability of normalizing the malignant phenotype of cancer cells, we have discovered RAP1A and RECK. RECK is decreased in many kinds of solid tumors, and when artificially expressed, it inhibits the ability of cancer cells to invade, metastasize, and recruit blood vessels (angiogenesis). Hence, our study of RECK may help developing new diagnostic and therapeutic methods. We have also shown that RAS oncogenes may be involved in differentiation and even tumor suppression depending on cell type. Through screening of genes up-regulated in early stages of brain development, we have discovered several novel molecules with interesting bio-activities such as Nedd2/caspase-2 (a protease executing apoptosis), Nedd4 (ubiquitin ligase), Nedd5/Sept2 (novel cytoskeletal protein involved in cell division), and Nedd8 (ubiquitin-related protein modifier).
In a friendly and inspiring atmosphere, graduate students with various backgrounds (including several foreign fellows) are struggling to solve the important puzzles of how cancer cells behave selfishly and how they can be tamed.


Molecular Oncology
Professor Makoto Noda
Associate
 Professor


Hitoshi Kitayama,
Yoko Yoshida
Assistant
 Professor


Tomoko Matsuzaki,
Takao Miki
TEL +81-75-751-4150
FAX +81-75-751-4159
e-mail mnodavirus.kyoto-u.ac.jp
URL http://www.users.iimc.kyoto-u.ac.jp/~z59192/
Activated RAS oncogenes induce neuronal differentiation in PC12 cells  (Nature 318: 73-75, 1985).
RAP1A/Krev1 encoding a low molecular weight G-protein was discovered as a transformation suppressor gene against an activated RAS oncogene (Cell 56: 77-84, 1989).
Another transformation suppressor gene RECK encodes a membrane-anchored regulator of matrix metalloproteinases (MMP). RECK is down-regulated in many cancers and suppresses tumor angiogenesis, invasion, and metastasis when expressed in such cancer cells (PNAS 95, 13221-13226, 1998; Cell 107: 789-800, 2001).
Laboratory members
Recent Publications
1. Wang H, Imamura Y, Ishibashi R, Chandana EP, Yamamoto M, Noda M. The Reck tumor suppressor protein alleviates tissue damage and promotes functional recovery after transient cerebral ischemia in mice. J Neurochem 115, 385-398 (2010).
2. Shamma A, Takegami Y, Miki T, Kitajima S, Noda M, Obara T, Okamoto T, Takahashi C. Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation. Cancer Cell 15, 255-269 (2009).
3. Omura A, Matsuzaki T, Mio K, Ogura T, Yamamoto M, Fujita A, Okawa K, Kitayama H, Takahashi C, Sato C, Noda M. RECK forms cowbell-shaped dimers and inhibits matrix metalloproteinase-catalyzed cleavage of fibronectin. J Biol Chem 284, 3461-3469 (2009).
4. Morioka Y, Monypenny J, Matsuzaki T, Shi S, Alexander DB, Kitayama H, Noda M. The membrane-anchored metalloproteinase regulator RECK stabilizes focal adhesions and anterior-posterior polarity in fibroblasts. Oncogene 28, 1454-1464 (2009).
5. Muraguchi T, Takegami Y, Ohtsuka T, Kitajima S, Chandana EP, Omura A, Miki T, Takahashi R, Matsumoto N, Ludwig A, Noda M, Takahashi C. RECK modulates Notch signaling during cortical neurogenesis by regulating ADAM10 activity. Nat Neurosci 10, 838-845 (2007).