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 - Basic Medicine (Core Departments) - Bioregulation
The cancer death rate is increasing every year, mostly due to invasion and metastasis. Accordingly, overcoming cancer invasion and metastasis should be on top of the agenda in today's research. To this end, we will need a wide-range basic research from molecular and cellular levels, to whole body studies aiming at novel therapeutic strategies. In our laboratory, we have constructed many mouse models of gastrointestinal polyposis and cancer. Using such models, we have proven the role of cyclooxygenase 2 (COX-2) in polyp formation and established the therapeutic strategy with COX-2 inhibitors. We are currently pursuing studies focusing on mouse models of invasive and metastatic cancers. Because of years of experience in research in USA by the principal investigator, special emphasis is placed on the graduate and postdoctoral training with international views.

  Makoto Mark Taketo, M.D., Ph.D.
Research and Education
In our laboratory, we have constructed many mouse tumor models, making extensive use of the transgenic and gene knockout technology. For example, we have constructed Apc-Δ(delta)716 knockout mice as a model for familial adenomatous polyposis (FAP). In this model, we discovered that COX-2 is induced at a very early stage, and contributes to the expansion of the polyps. We have also developed a mouse model of colon cancer (adenocarcinoma) that shows strong invasion. Using this model, we have recently reported that the cancer epithelium, where the TGF-β(beta) family signaling is inactivated, expresses a chemokine ligand and attracts bone marrow-derived immature myeloid cells that produce proteases and help the tumor epithelium invasion. Based on these achievements, we are currently pursuing the following research projects.

1) Identification of genes that regulate malignant progression
2) Role of iMCs in colon cancer invasion and metastasis
3) Analysis of signaling pathways that are essential for tumorigenesis
4) Pre-clinical study for cancer therapy

In pursuing these research projects, we focus on training of young scientists in a wide variety of techniques in recombinant DNA technology, embryonic stem cell culture and homologous recombination, mouse embryo manipulation, mouse genetics, histopathology, and pharmacology as well as up-to-date knowledge in the related fields.

Professor Makoto Mark Taketo

Masahiro Sonoshita

Teruaki Fujishita
TEL +81-75-753-4477
FAX +81-75-753-4402
Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling
Stimulation of colon cancer invasion and metastasis by immature myeloid cells (iMCs)
Recent Publications
1. Taketo MM. Roles of stromal microenvironment in colon cancer progression. J. Biochem. 151:477-481, 2012.
2. Fujishita T, Aoki M, Taketo MM. JNK signaling promotes intestinal tumorigenesis through activation of mTOR complex 1 in Apc(Δ716) mice. Gastroenterology 140: 1556-1563, 2011.
3. Sonoshita M, Aoki M, Fuwa H, Aoki K, Hosogi H, Sakai Y, Hashida H, Takabayashi A, Sasaki M, Robine S, Itoh K, Yoshioka K, Kakizaki F, Kitamura T, Oshima M, Taketo MM. Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling. Cancer Cell 19:125-137, 2011.
4. Aoki K, Kakizaki F, Sakashita H, Manabe T, Aoki M, Taketo MM. Suppression of Colonic Polyposis by Homeoprotein CDX2 through its Nontranscriptional Function that Stabilizes p27Kip1. Cancer Res. 71:593-602, 2011.
5. Kitamura T, Fujishita T, Loetscher P, Revesz L, Hashida H, Kizaka-Kondoh S, Aoki M, Taketo MM. Inactivation of che mokine (C-C motif) receptor 1 (CCR1) suppresses colon cancer liver metastasis by blocking accumulation of immature myeloid cells in a mouse model. Proc. Natl. Acad. Sci. USA 107:13063-13068, 2010.