Graduate School of Medicine „ Human Science
„ Molecular Oncology



Professor: Suhn'ichiro TANIGUCHI
Associate Professor: Shigeaki HIDA

Summary of Activity
Our goal is to understand characteristics of cancer with molecular and cellular biological terms and to apply the acquired knowledge to clinical diagnosis and treatment of cancer.
Thus our activity is basically directed at cancer patients. On one hand, we would like to enjoy it, because through the research activity we can learn the beautiful mechanism of human life.


Research Projects
  • We found ASC (Apoptosis associated Speck-like protein containing a CARD) which is intimately involved in inflammation, apoptosis. ASC seems to be a good probe to study carcinogenesis from the inflammatory and apoptotic point of view. In addition, ASC gene is epigenetically regulated by the methylation of CpG island. Thus, ASC study may lead us also to understand the instability of cancer phenotype, one of the most important issues in cancer research.
  • Analysis of innate sensing for the regulation of immune responses. Host defense in our body consists of the innate immunity and the acquired immunity. These two arms of the immunity are mediated by different components of the immune system to eliminate different types of microbes. Innate immune cells resident in tissues gsenseh the products (DNA, LPS, protease etc.) of pathogens, allergens or tumor cells, and instruct how the acquired immune system respond, thereby playing critical roles in responses to those foreign and internal invaders. Although this sensing is generally beneficial to our body, its excessive and/or erroneous activation sometimes induces autoimmune and other inflammatory disorders including tumor progression. The goal of our laboratory is to understand the molecular mechanisms of these immune sensor systems and the pathogenesis of chronic inflammatory diseases and ultimately develop novel strategies for these diseases.
  • We found that actin-binding protein, calponin, attacks cancer cells and simultaneously protects the host from invasion.
  • We found a nuclear protein, Scapinin, which binds and inhibits the activity of protein phsophatase 1. This protein also binds to actin, seemingly being useful to understand the scaffold system of signal transduction for cell growth and differentiation.
  • We have proposed a treatment of solid tumors using non-pathogenic and anaerobic bacteria as drug delivery system by directing our attention to hypoxia in solid tumors. A venture company has been founded to develop newly designed drugs.
References

  1. Taniguchi S, Fujimori M, Sasaki T, Tsutsui H, Shimatani Y, Seki K, Amano J.
    Targeting solid tumors with non-pathogenic obligate anaerobic bacteria.
    Cancer Sci. 2010 May 22. [Epub ahead of print]

  2. Nakajima K, Takeoka M, Mori M, Hashimoto S, Sakurai A, Nose H, Higuchi K, Itano N,Shiohara M, Oh T, Taniguchi S.
    Exercise Effects on Methylation of ASC Gene.
    Int J Sports Med. 30:1-5, 2010

  3. Hida S, Yamasaki S, Sakamoto Y, Takamoto M, Obata K, Takai T, Karasuyama H, Sugane K, Saito T, Taki S.
    Fc receptor gamma-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils.
    Nat Immunol. 10(2):214-22, 2009

  4. Sagara J, Arata T, Taniguchi S
    Scapinin, the Protein Phosphatase 1 Binding Protein, Enhances Cell Spreading and Motility by Interacting with the Actin Cytoskeleton.
    PLoS ONE 4(1):e4247, 2009

  5. Yajima N, Takahashi M, Morimoto H, Shiba Y, Takahashi Y, Masumoto J, Ise H, Sagara J, Nakayama J, Taniguchi S, Ikeda U.
    Critical role of bone marrow apoptosis-associated speck-like protein, an inflammasome adaptor molecule, in neointimal formation after vascular injury in mice.
    Circulation. 2008 Jun 17;117(24):3079-87.

  6. Koyama H, Hibi T, Isogai Z, Yoneda M, Fujimori M, Amano J,Kawakubo M, Kannagi R, Kimata K, Taniguchi S, Itano N.
    Hyperproduction of Hyaluronan in Neu-induced Mammary Tumor Accelerates Angiogennesis through Stromal Cell Recruitmet.
    Am.J. Pathol.170:1086-1099, 2007

  7. Taniguchi S, Sagara J.
    Regulatory molecules involved in inflammasome formation with special reference to a key mediator protein, ASC.
    Semin Immunopathol. 29(3):231-238. Epub2007 Sep 6. (review)

  8. Yu JW, Wu J, Zhang Z, Datta P, Ibrahimi I, Taniguchi S, Sagara J, Fernandes-Alnemri T, Alnemri ES.
    Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization.
    Cell Death Differ. 2006 Feb;13(2):236-49.

  9. Machida EO, Brock MV, Hooker CM, Nakayama J, Ishida A, Amano J, Picchi MA, Belinsky SA, Herman JG, Taniguchi S, Baylin SB.
    Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer.
    Cancer Res. 2006.

  10. Taniguchi S.
    Suppression of cancer phenotypes through a multifunction actin binding protein, calponin,that attacks cancer cells and simultaneously protects the host from invasion.
    Cancer Science 96:738-746,2005 (review)