Theme

The goal of our research is to understand the molecular mechanisms of cell proliferation, tumorigenesis and senescence.

About Research

Cell growth, tumorigenesis and senescence

Our research is concentrated in the following areas:
１．Tumor heterogeneity
Recent studies suggest that a subpopulation within the tumor mass, called cancer stem cells, has high tumorigenic potential. Therefore, cancer stem cells could be critical targets for cancer chemotherapy. We are focusing our investigation on the elucidation of the molecular mechanisms of cancer stem cell self-renewal and differentiation. We are  also analyzing the interaction of cancer stem cells with immune cells and cancer-sociated fibroblasts.

２．Analysis of long-lived mutant mice
Mice deficient for D8 live longer than wild-type mice. We are investigating the role of D8 in aging and senescence.

３．Autism and socio-emotional learning
The onest of autism is thought to be closely tied to the dysfunction of the amygdala, but the molecular mechanisms liking the impaired function of this region to autistic behavior are not well-understood. We are exploring the functions of the autism-related protein PX-RICS in emotional learning in the amygdala.

Single cell analysis of tumor heterogeneity
Glioblastoma stem cells lose their tumorigenic capacity under serumcontaining culture conditions.

Publication

  1. Funato, K., Echizen, K., Hayashi, T., Koyama-Nasu, R., Nasu-Nishimura, Y., Morishita, Y., Kishi, Y., Gotoh, Y., Tabar, V., Todo, T., Ino, Y., Mukasa, A., Saito, A. and Akiyama, T. Histone deacetylase SIRT2-mediated inactivation of p73 is required for the proliferation and tumorigenicity of glioblastoma cells. under revision. EMBO Rep. 2018 Sep 13. pii: e45587. doi: 10.15252/embr.201745587.
  2. Yamazumi Y., Sasaki O., Imamura M., Oda T., Ohno Y., Shiozaki-Sato Y., Nagai S., Suyama S., Kamoshida Y., Funato K., Yasui T., Kikutani H., Yamamoto K., Dohi M., Koyasu S., Akiyama T. The RNA-binding protein Mex-3B is required for IL-33 induction in the development of allergic airway inflammation. Cell Rep. 16:2456-71 (2016).
  3. Taniue K., Kurimoto A., Takeda Y., Nagashima T., Okada-Hatakeyama M., Kato Y., Shirahige K., Akiyama T. ASBEL-TCF3 complex is required for the tumorigenicity of colorectal cancer cells. Proc. Natl. Acad. Sci. USA 113: 12739-12744 (2016)
  4. Kawasaki Y., Komiya M., Matsumura K., Negishi L., Suda S., Okuno M., Yokota N., Osada T., Nagashima T., Hiyoshi M., Okada-Hatakeyama M., Kitayama J., Shirahige K., Akiyama T. MYU, a novel target lncRNA for Wnt/c-Myc signaling, mediates induction of CDK6 to promote cell cycle progression. Cell Rep 16: 2554-64 (2016).
  5. Taniue K., Kurimoto A., Sugimasa H., Nasu E., Takeda Y., Iwasaki K., Nagashima T., Okada-Hatakeyama M., Oyama M., Kozuka-Hata H., Hiyoshi M., Kitayama J., Negishi L., Kawasaki Y., Akiyama T. Long non-coding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1. Proc. Natl. Acad. Sci. USA. 113(5):1273-8127 (2016).
  6. Nakamura T., Arima-Yoshida F., Sakaue F., Nasu-Nishimura Y., Takeda Y., Matsuura K., Akshoomoff N., Mattson S.N., Grossfeld P.D., Manabe T. Akiyama T. PX-RICS-deficient mice mimic autism spectrum disorder in Jacobsen syndrome through impaired GABAA receptor trafficking. Nat. Commun. 2016 Mar 16;7:10861. doi: 10.1038/ncomms10861.
  7. Tsuji, S., Kawasaki, Y., Furukawa, S., Taniue, K., Hayashi, T., Okuno, M., Hiyoshi, M., Kitayama, J., Akiyama, T. The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumorigenesis. Nat. Commun. 2014;5:3150. doi: 10.1038/ncomms4150.
  8. Matsuura, K., Jigami, T., Taniue, K., Morishita, Y., Adachi, A., Senda, T., Nonaka, A., Aburatani, H., Nakamura, T. and Akiyama, T. Identification of a link between Wnt/b-catenin signaling and the cell fusion pathway. Nat. Commun. 2011 Nov 22;2:548. doi: 10.1038/ncomms1551.
  9. Kawasaki, Y., Tsuji, S., Muroya, K., Furukawa, S., Shibata, Y., Okuno, M., Ohwada, S. and Akiyama, T. The APC-associated exchange factors Asef and Asef2 are required for adenoma formation in ApcMin/+ mice. EMBO Rep. 10, 1355-1362 (2009).
  10. Nakamura T., Hayashi T., Yukiko Nasu-Nishimura Y., Sakaue F., Okabe T., Ohwada S., Matsuura K., Akiyama T. PX-RICS mediates ER-to-Golgi transport of the N-cadherin/β-catenin complex. Genes Dev. 22, 1244-1256 (2008).
Tetsu Akiyama
Project Professor
Ph.D.
Yoshihiro Kawasaki
Visiting Associate Professor
Ph.D.
Tsutomu Nakamura
Visiting Associate Professor
Ph.D.