Aurora Laboratory's Home Page

MASAAKI TATSUKA                                                      

PROFESSOR, RADIATION GENOME SYSTEMS BIOLOGY

Research topics                                                                                                    

   Our studies currently aim to answer the following questions: What are the regulatory proteins during mitosis under both normoxia and hypoxia conditions? What are the mechanisms underlying anoikis (a form of programmed cell death which is induced by anchorage- dependent cells detaching from the surrounding extracellular matrix) resistance of metastatic cancer cells? What are the signaling molecules to induce perturbation of cell polarity by ionizing radiation and UV?

   In addition, we are testing whether 'ABITAN', a bio-dosimetry system developed by us to evaluate the absorbed dose of ionizing radiation, is useful for the Fukushima Daiichi nuclear disaster.


Outline of Research

   The principal object of our research is to know the true nature of genome homeostasis maintenance mechanism and the fundamental basis of the continuity of genetic information. In multicellular organism especially in animal, the perturbation of genome integrity leads cells to programmed cell death, and occasionally leads them to neoplasm.

   We are focusing into three 'sis's, namely metastasis, mitosis, and apoptosis: 1) how do cancer cells get anoikis resistance during metastasis processes? 2) how do cancer cells proceed mitosis under hypoxia condition? 3) how do epithelial cells lose cell polarity during radiation injury?

   For first question, we are studying the chromosomal passenger proteins (CPPs), Aurora-B, Survivin, INCENP, and Borealin, and their related proteins. In  solid tumor, invaded cells have to survive after intravasation or penetration for  lymphnode metastasis, distant metastasis, and peritoneal metastasis. Anoikis resistance is an essential part of the metastasized cells. CPPs and their related proteins crucially function for this phenotype. For second question, we have found hypoxia-specific expression of several mitotic proteins. Hypoxia is niche for aggressive cancer cells. In our hypothesis, the regulation mechanisms of mitotic processes differ between normoxia and hypoxia.  For third question, we are studying the small GTPases and their regulators. When irradiated, the cells induce apoptosis signaling. Caspase-3 is a major factor for apoptosis execution. RhoGDIbeta, One of its substrates, produces a truncated form. We have found that this truncation is critical to lose cell polarity after irradiation. This mechanism may possibly explain how radiation affects the epithelium structure and also how the immune system is vulnerable to radiation. 


・2017 Research Focus (Japanese)

・2017 Research Focus (English)

・2017 inovation information (Japanese)

・2017 I conduct a class entirely in English.


Selected Publication                                                                                             

Ota T, Jiang YS, Fujiwara M, Tatsuka M. Apoptosis‑independent cleavage of RhoGDIβ at Asp19 during PMA‑stimulated differentiation of THP‑1 cells to macrophages. Mol Med Rep. 2017 Apr;15(4):1722-1726. doi: 10.3892/mmr.2017.6199.


Wiedemuth R, Klink B, Fujiwara M, Schröck E, Tatsuka M, Schackert G, Temme A. Janus face-like effects of Aurora B inhibition: antitumoral mode of action versus induction of aneuploid progeny. Carcinogenesis. 2016 Oct;37(10):993-1003. doi: 10.1093/carcin/bgw083.


Qi G, Kudo Y, Tang B, Liu T, Jin S, Liu J, Zuo X, Mi S, Shao W, Ma X, Tsunematsu T, Ishimaru N, Zeng S, Tatsuka M, Shimamoto F. PARP6 acts as a tumor suppressor via downregulating Survivin expression in colorectal cancer. Oncotarget. 2016 Feb 25. doi: 10.18632/oncotarget.7712.


Tatsuka M, Fujiwara M, Okamoto M, Hori M, Sugihara Y, Jikihara H, Nakaoji K, Hamada K, Suga H, Shimamoto F. Possibility of RhoGDIβ as a molecular target for biomedical applications. J Life Environ Sci. 2016 March;6(1):(in press).


Fujiwara M, Okamoto M, Hori M, Suga H, Jikihara H, Sugihara Y, Shimamoto F, Mori T, Nakaoji K, Hamada K, Ota T, Wiedemuth R, Temme A, Tatsuka M. Radiation-Induced RhoGDIβ Cleavage Leads to Perturbation of Cell Polarity: A Possible Link to Cancer Spreading. J Cell Physiol. 2016 Feb 25. doi: 10.1002/jcp.25362.


Ota T, Maeda M, Okamoto M, Tatsuka M. Positive regulation of Rho GTPase activity by RhoGDIs as a result of their direct interaction with GAPs. BMC Syst Biol. 2015 Jan 28;9:3. doi: 10.1186/s12918-015-0143-5.


Okamoto M, Fujiwara M, Hori M, Okada K, Yazama F, Konishi H, Xiao Y, Qi G, Shimamoto F, Ota T, Temme A, Tatsuka M. tRNA Modifying Enzymes, NSUN2 and METTL1, Determine Sensitivity to 5-Fluorouracil in HeLa Cells. PLoS Genet. 2014 Sep 18;10(9):e1004639.


Wiedemuth R, Klink B, Töpfer K, Schröck E, Schackert G, Tatsuka M, Temme A. Survivin safeguards chromosome numbers and protects from aneuploidy independently from p53. Mol Cancer. 2014 May 9;13:107.


Hori M, Miki T, Okamoto M, Yazama F, Konishi H, Kaneko H, Shimamoto F, Ota T, Temme A, Tatsuka M. The detergent-soluble cytoplasmic pool of Survivin suppresses anoikis and its expression is associated with metastatic disease of human colon cancer. PLoS One. 2013;8(2):e55710.


Okamoto M, Fukutomi R, Hori M, Tsuno T, Fujii M, Tatsuka M. Evaluation of carcinogenic/co-carcinogenic activity of mokusaku-eki, a wood charcoal by-product used as a folk remedy, in BALB/c 3T3 cells. J Life Environ Sci. 2013 March;5(1):9-17.


Jiang Y-S, Maeda M, Okamoto M, Fujii M, Fukutomi R, Hori M, Tatsuka M. Centrosomal localization of RhoGDIβ and its relevance to mitotic processes in cancer cells. Int J Oncol. 2013 Feb;42(2):460-8.


Tuncel H, Tanaka S, Oka S, Nakai S, Fukutomi R, Okamoto M, Ota T, Kaneko H, Tatsuka M, Shimamoto F. PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer. Int J Oncol. 2012 Dec;41(6):2079-86.


Tuncel H, Shimamoto F, Qi G, Aoki E, Jikihara H, Nakai S, Takata T, Tatsuka M. Nuclear Aurora B and cytoplasmic Survivin expression is involved in lymph node metastasis of colorectal cancer.   Oncol Lett. 2012 May;3(5):1109-1114.


Okamoto M, Koga S, Fujii M, Koya S, Shimamoto F, Matuda N, Tatsuka M. Radiation in food: Current estimates of the health effects of low-dose ionizing radiation from contaminated food and drink caused by the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant accident. New Food Industry 2012 May;3(3):1-17.


Tatsuka M, Takata T. Substrate of Aurora kinase B (SAKI): its application. Japanese Patent No. 4919457 (applicant: Hiroshima University). 2012. Japanese.


Okamoto M, Hirata S, Sato S, Koga S, Fujii M, Qi G, Ogawa I, Takata T, Shimamoto F, Tatsuka M. Frequent increased gene copy number and high protein expression of tRNA (cytosine-5-)-methyltransferase (NSUN2) in human cancers. DNA Cell Biol. 2012 May;31(5):660-71.


Tatsuka M. ABITAN: a novel bio-dosimetry system. Japanese Patent No. 4853866 (applicant: Hiroshima University). 2012. Japanese.


Okamoto M, Fujii M, Tatsuka M. Overview of Aurora kinases. Seitai-no-Kagaku. 2011 May;62(5):464-5. Japanese.


Okamoto M, Fujii M, Tatsuka M. Chromosomal passenger complex: its structure and function. Seitai-no-Kagaku. 2011 May;62(5):460-3. Japanese.


Temme A, Geiger KD, Wiedemuth R, Conseur K, Pietsch T, Felsberg J, Reifenberger G, Tatsuka M, Hagel C, Westphal M, Berger H, Simon M, Weller M, Schackert G. Giant cell glioblastoma is associated with altered aurora b expression and concomitant p53 mutation. J Neuropathol Exp Neurol. 2010 Jun;69(6):632-42.


Okamoto M, Koga S, Tatsuka M. Differential regulation of caspase-9 by ionizing radiation- and UV-induced apoptotic pathways in thymic cells. Mutat Res. 2010 Jun 1;688(1-2):78-87.


Qi G, Tuncel H, Aoki E, Tanaka S, Oka S, Kaneko I, Okamoto M, Tatsuka M, Nakai S, Shimamoto F. Intracellular localization of survivin determines biological behavior in colorectal cancer. Oncol Rep. 2009 Sep;22(3):557-62.


Tatsuka M, Sato S, Kanda A, Miki T, Kamata N, Kitajima S, Kudo Y, Takata T. Oncogenic role of nuclear accumulated Aurora-A. Mol Carcinog. 2009 Sep;48(9):810-20.


Tatsuka M. Aurora kinases: new targets for cancer chemotherapy. J Clin Exp Med (Igaku-no-Ayumi). 2008 May;224(1):87-92. Japanese.


Kitajima S, Kudo Y, Ogawa I, Tatsuka M, Kawai H, Pagano M, Takata T. Constitutive phosphorylation of aurora-a on ser51 induces its stabilization and consequent overexpression in cancer. PLoS One. 2007 Sep 26;2(9):e944.


Qi G, Ogawa I, Kudo Y, Miyauchi M, Siriwardena BS, Shimamoto F, Tatsuka M, Takata T. Aurora-B expression and its correlation with cell proliferation and metastasis in oral cancer. Virchows Arch. 2007 Mar;450(3):297-302.


Sakita-Suto S, Kanda A, Suzuki F, Sato S, Takata T, Tatsuka M. Aurora-B regulates RNA methyltransferase NSUN2. Mol Biol Cell. 2007 Mar;18(3):1107-17.


Ota T, Maeda M, Murakami M, Takegami T, Suto S, Tatsuka M. Activation of Rac1 by Rho-guanine nucleotide dissociation inhibitor-beta with defective isoprenyl-binding pocket. Cell Biol Int. 2007 Jan;31(1):92-6.


Tanno Y, Kobayashi K, Tatsuka M, Gotoh E, Takakura K. Mitotic arrest caused by an X-ray microbeam in a single cell expressing EGFP-aurora kinase B. Radiat Prot Dosimetry. 2006;122(1-4):301-6.


Ota T, Maeda M, Sakita-Suto S, Zhou X, Murakami M, Takegami T, Tatsuka M. RhoGDIbeta lacking the N-terminal regulatory domain suppresses metastasis by promoting anoikis in v-src-transformed cells. Clin Exp Metastasis. 2006;23(7-8):323-34. 


Kanda A, Kawai H, Suto S, Kitajima S, Sato S, Takata T, Tatsuka M. Aurora-B/AIM-1 kinase activity is involved in Ras-mediated cell transformation. Oncogene. 2005 Nov 10;24(49):7266-72.


Tatsuka M, Sato S, Kitajima S, Suto S, Kawai H, Miyauchi M, Ogawa I, Maeda M, Ota T, Takata T. Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis. Oncogene. 2005 Feb 3;24(6):1122-7.


Sasai K, Katayama H, Stenoien DL, Fujii S, Honda R, Kimura M, Okano Y, Tatsuka M, Suzuki F, Nigg EA, Earnshaw WC, Brinkley WR, Sen S. Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Cell Motil Cytoskeleton. 2004 Dec;59(4):249-63.


Zhou X, Suto S, Ota T, Tatsuka M. Nuclear translocation of cleaved LyGDI dissociated from Rho and Rac during Trp53-dependent ionizing radiation-induced apoptosis of thymus cells in vitro. Radiat Res. 2004 Sep;162(3):287-95.


Araki K, Nozaki K, Ueba T, Tatsuka M, Hashimoto N. High expression of Aurora-B/Aurora and Ipll-like midbody-associated protein (AIM-1) in astrocytomas. J Neurooncol. 2004 Mar-Apr;67(1-2):53-64.


Ota T, Maeda M, Suto S, Tatsuka M. LyGDI functions in cancer metastasis by anchoring Rho proteins to the cell membrane. Mol Carcinog. 2004 Apr;39(4):206-20.


Zhang Y, Nagata Y, Yu G, Nguyen HG, Jones MR, Toselli P, Jackson CW, Tatsuka M, Todokoro K, Ravid K. Aberrant quantity and localization of Aurora-B/AIM-1 and survivin during megakaryocyte polyploidization and the consequences of Aurora-B/AIM-1-deregulated expression. Blood. 2004 May 15;103(10):3717-26.


Yasui Y, Urano T, Kawajiri A, Nagata K, Tatsuka M, Saya H, Furukawa K, Takahashi T, Izawa I, Inagaki M. Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis. J Biol Chem. 2004 Mar 26;279(13):12997-3003.


Minoshima Y, Kawashima T, Hirose K, Tonozuka Y, Kawajiri A, Bao YC, Deng X, Tatsuka M, Narumiya S, May WS Jr, Nosaka T, Semba K, Inoue T, Satoh T, Inagaki M, Kitamura T. Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis. Dev Cell. 2003 Apr;4(4):549-60.


Kawajiri A, Yasui Y, Goto H, Tatsuka M, Takahashi M, Nagata K, Inagaki M. Functional significance of the specific sites phosphorylated in desmin at cleavage furrow: Aurora-B may phosphorylate and regulate type III intermediate filaments during cytokinesis coordinatedly with Rho-kinase. Mol Biol Cell. 2003 Apr;14(4):1489-500.


Temme A, Rieger M, Reber F, Lindemann D, Weigle B, Diestelkoetter-Bachert P, Ehninger G, Tatsuka M, Terada Y, Rieber EP. Localization, dynamics, and function of survivin revealed by expression of functional survivinDsRed fusion proteins in the living cell. Mol Biol Cell. 2003 Jan;14(1):78-92.


Goto H, Yasui Y, Kawajiri A, Nigg EA, Terada Y, Tatsuka M, Nagata K, Inagaki M. Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation in the cytokinetic process. J Biol Chem. 2003 Mar 7;278(10):8526-30.


Ota T, Maeda M, Tatsuka M. Cationic liposomes with plasmid DNA influence cancer metastatic capability. Anticancer Res. 2002 Nov-Dec;22(6C):4049-52.


Ota T, Suto S, Katayama H, Han ZB, Suzuki F, Maeda M, Tanino M, Terada Y, Tatsuka M. Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability. Cancer Res. 2002 Sep 15;62(18):5168-77.


Kimura Y, Suto S, Tatsuka M. Evaluation of carcinogenic/co-carcinogenic activity of chikusaku-eki, a bamboo charcoal by-product used as a folk remedy, in BALB/c 3T3 cells. Biol Pharm Bull. 2002 Aug;25(8):1026-9.


Ueda K, Murata-Hori M, Tatsuka M, Hosoya H. Rho-kinase contributes to diphosphorylation of myosin II regulatory light chain in nonmuscle cells. Oncogene. 2002 Aug 29;21(38):5852-60.


Murata-Hori M, Tatsuka M, Wang YL. Probing the dynamics and functions of aurora B kinase in living cells during mitosis and cytokinesis. Mol Biol Cell. 2002 Apr;13(4):1099-108.


Tatsuka M, Maeda M, Ota T. Anticarcinogenic effect and enhancement of metastatic potential of BALB/c 3T3 cells by ginsenoside Rh(2). Jpn J Cancer Res. 2001 Nov;92(11):1184-9.


Katayama H, Zhou H, Li Q, Tatsuka M, Sen S. Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle. J Biol Chem. 2001 Dec 7;276(49):46219-24.


Ota T, Maeda M, Tanino M, Tatsuka M. Functional suppression of integrin beta 4-mediated adhesion caused by in vivo sequential selection for cancer cell intravasation. Anticancer Res. 2001 Jan-Feb;21(1A):205-11.


Kawasaki A, Matsumura I, Miyagawa Ji, Ezoe S, Tanaka H, Terada Y, Tatsuka M, Machii T, Miyazaki H, Furukawa Y, Kanakura Y. Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells. J Cell Biol. 2001 Jan 22;152(2):275-87.


Murata-Hori M, Fumoto K, Fukuta Y, Iwasaki T, Kikuchi A, Tatsuka M, Hosoya H. Myosin II regulatory light chain as a novel substrate for AIM-1, an aurora/Ipl1p-related kinase from rat. J Biochem. 2000 Dec;128(6):903-7.


Lu Y, Tatsuka M, Takebe H, Yagi T.Involvement of cyclin-dependent kinases in doxorubicin-induced apoptosis in human tumor cells. Mol Carcinog. 2000 Sep;29(1):1-7. 


Kawai H, Ota T, Suzuki F, Tatsuka M. Molecular cloning of mouse thioredoxin reductases. Gene. 2000 Jan 25;242(1-2):321-30. 


Kawai H, Yamada Y, Tatsuka M, Niwa O, Yamamoto K, Suzuki F. Down-regulation of nuclear factor kappaB is required for p53-dependent apoptosis in X-ray-irradiated mouse lymphoma cells and thymocytes. Cancer Res. 1999 Dec 15;59(24):6038-41.


Ota T, Maeda M, Tatsuka M, Matsui T, Tanino M, Tanaka T. Decrease of metastatic ability after selection for intravasating ability in Lewis lung carcinoma (3LL) cell line. Cancer Lett. 1999 May 3;139(1):105-8.


Katayama H, Ota T, Jisaki F, Ueda Y, Tanaka T, Odashima S, Suzuki F, Terada Y, Tatsuka M. Mitotic kinase expression and colorectal cancer progression. J Natl Cancer Inst. 1999 Jul 7;91(13):1160-2.


Katayama H, Ota T, Morita K, Terada Y, Suzuki F, Katoh O, Tatsuka M. Human AIM-1: cDNA cloning and reduced expression during endomitosis in megakaryocyte-lineage cells. Gene. 1998 Dec 11;224(1-2):1-7.


Tatsuka M, Katayama H, Ota T, Tanaka T, Odashima S, Suzuki F, Terada Y. Multinuclearity and increased ploidy caused by overexpression of the aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells. Cancer Res. 1998 Nov 1;58(21):4811-6.


Terada Y, Tatsuka M, Suzuki F, Yasuda Y, Fujita S, Otsu M. AIM-1: a mammalian midbody-associated protein required for cytokinesis. EMBO J. 1998 Feb 2;17(3):667-76.


Kawai H, Kitamura Y, Nikaido O, Tatsuka M, Hama-Inaba H, Muto M, Ohyama H, Suzuki F. Isolation and characterization of apoptosis-resistant mutants from a radiosensitive mouse lymphoma cell line. Radiat Res. 1998 Jan;149(1):41-51.


Izumi T, Tatsuka M, Tano K, Asano M, Mitra S. Molecular cloning and characterization of the promoter of the human N-methylpurine-DNA glycosylase (MPG) gene. Carcinogenesis. 1997 Sep;18(9):1837-9.


Tatsuka M, Ota T, Maeda M, Wada M, Yamagishi N, Taniguchi S, Seiki M, Odashima S. A BALB/c 3T3-transformed cell line suitable for transfection assay of metastasis-inducing genes. Int J Cancer. 1997 Mar 28;71(1):88-93.


Ota T, Maeda M, Odashima S, Ninomiya-Tsuji J, Tatsuka M. G1 phase-specific suppression of the Cdk2 activity by ginsenoside Rh2 in cultured murine cells. Life Sci. 1997;60(2):PL39-44.


Tatsuka M, Ota T, Yamagishi N, Kashihara Y, Wada M, Matsuda N, Mitsui H, Seiki M, Odashima S. Different metastatic potentials of ras- and src-transformed BALB/c 3T3 A31 variant cells. Mol Carcinog. 1996 Apr;15(4):300-8.


Tatsuka M, Yamagishi N, Wada M, Mitsui H, Ota T, Odashima S. Electroporation-mediated transfection of mammalian cells with crude plasmid DNA preparations. Genet Anal. 1995 Oct;12(2):113-7.


Terada Y, Tatsuka M, Jinno S, Okayama H. Requirement for tyrosine phosphorylation of Cdk4 in G1 arrest induced by ultraviolet irradiation. Nature. 1995 Jul 27;376(6538):358-62.


Tatsuka M, Ibeanu GC, Izumi T, Narayan S, Ramana CV, Kim NK, Kang W, Roy G, Mitra S. Structural organization of the mouse DNA repair gene, N-methylpurine-DNA glycosylase. DNA Cell Biol. 1995 Jan;14(1):37-45.


Wada M, Ihara Y, Tatsuka M, Mitsui H, Kohno K, Kuwano M, Schlessinger D. HPRT yeast artificial chromosome transfer into human cells by four methods and an involvement of homologous recombination. Biochem Biophys Res Commun. 1994 May 16;200(3):1693-700.


Tatsuka M, Mitsui H, Wada M, Nagata A, Nojima H, Okayama H. Elongation factor-1 alpha gene determines susceptibility to transformation. Nature. 1992 Sep 24;359(6393):333-6.


Tatsuka M, Owada MK, Mitsui H. Expression of platelet-derived growth factor-independent phenotypes in BALB/c 3T3 cell variant with high susceptibility to chemically or physically induced neoplastic cell transformation: dissociation from activation of protein kinase C. Cancer Res. 1992 Aug 1;52(15):4232-41.


Shiraishi T, Owada MK, Tatsuka M, Fuse Y, Watanabe K, Kakunaga T. A tyrosine-specific protein kinase inhibitor, alpha-cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamide, blocks the phosphorylation of tyrosine kinase substrate in intact cells. Jpn J Cancer Res. 1990 Jun-Jul;81(6-7):645-52.


Taniguchi S, Tatsuka M, Nakamatsu K, Inoue M, Sadano H, Okazaki H, Iwamoto H, Baba T. High invasiveness associated with augmentation of motility in a fos-transferred highly metastatic rat 3Y1 cell line. Cancer Res. 1989 Dec 1;49(23):6738-44.


Tatsuka M, Jinno S, Owada MK, Kakunaga T. A digital image processing system for quantitating dynamic morphology in cultured mammalian cells. Exp Cell Res. 1989 Dec;185(2):342-52. Erratum in: Exp Cell Res 1990 Apr;187(2):349.


Tatsuka M, Nikaido O, Tatsumi K, Takebe H. X-ray-induced G2 arrest in ataxia telangiectasia lymphoblastoid cells. Mutat Res. 1989 Oct;214(2):321-8.


Shiraishi T, Owada MK, Tatsuka M, Yamashita T, Watanabe K, Kakunaga T. Specific inhibitors of tyrosine-specific protein kinases: properties of 4-hydroxycinnamamide derivatives in vitro. Cancer Res. 1989 May 1;49(9):2374-8.


Tatsuka M, Jinno S, Kakunaga T. Quantitative measurement of cell motility associated with transformed phenotype. Jpn J Cancer Res. 1989 May;80(5):408-12.


Tatsuka M, Orita S, Kakunaga T. Analysis of cell variants showing differential susceptibilities to radiation- or chemical-induced neoplastic transformation: differences in their responses to growth factors. J Cell Physiol. 1989 Apr;139(1):18-23.


Tatsuka M, Orita S, Yagi T, Kakunaga T. An improved method of electroporation for introducing biologically active foreign genes into cultured mammalian cells. Exp Cell Res. 1988 Sep;178(1):154-62.


Ota T, Tahara M, Tatsuka M, Abe H, Odashima S. An approach to prolongation of survival rate in tumor bearing mice using 5-fluorouracil in combination with various kinds of herb medicine. Gan To Kagaku Ryoho. 1983 Aug;10(8):1858-65. Japanese.

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