Yasuyuki Fujita MD & PhD
At the initial stage of carcinogenesis, what happens when transformation occurs in single cells within epithelia? Using newly established mammalian epithelial cell lines and mouse model systems, we have demonstrated that normal epithelial cells and the newly emerging transformed cells often compete with each other for survival, a process called cell competition. Consequently, transformed cells are eliminated from epithelial tissues. These results imply that normal epithelial cells are able to eliminate the surrounding transformed cells; this concept potentially leads to a novel type of cancer preventive medicine.
Research and Education
Our studies have revealed that cell competition occurs at the interface between normal and transformed epithelial cells. Consequently, transformed cells often become losers and are eliminated from epithelial tissues via apical extrusion or cell death (Hogan et al., 2009, Nature Cell Biology) (Fig. 1). During the process of cell competition, normal cells recognize the presence of neighboring transformed cells and actively eliminate them from the cell society. This indicates that normal epithelia have anti-tumor activity that does not involve immune systems. We term this phenomenon EDAC (Epithelial Defense Against Cancer) (Kajita et al., 2014, Nature Communications) (Fig. 2). The next question is how epithelial cells recognize the differences from each other. Using various screening approaches, we are now trying to identify molecules that are involved in intercellular recognition machinery.The lab members acquire techniques of cell biology, biochemistry and mouse (or drosophila) genetics. Through the various intra- or inter-lab meetings, presentation and scientific communication skills are trained. We aim to issue world-leading next generation scientists from Yasu lab.
|(Fig. 1) Upon cell competition against normal epithelial cells,
transformed cells (red arrows) are apically extruded from the epithelial layer.
|(Fig. 2) Molecular mechanisms of EDAC.|
- Takeuchi, Y., Narumi,R., Akiyama, R., Vitiello, E., Shirai, T., Tanimura, N., Kuromiya, K., Ishikawa, S., Kajita, M., Tada, M., Haraoka, Y., Akieda, Y., Ishitani, T., Fujioka, Y., Ohba, Y., Yamada, S., Hosokawa, Y., Toyama, Y., Matsui, T., and Fujita, Y. (2020) Calcium wave promotes cell extrusion. Current Biology, 30(4); 670-681.
- Sasaki, A., Nagatake,T., Egami, R., Gu, G., Takigawa, I., Ikeda, W., Nakatani, T., Kunisawa, J. and Fujita, Y. (2018) Obesity suppresses cell competition-mediated apical elimination of RasV12-transformed cells from epithelial tissues. Cell Reports, 23(4):974-982.
- Kon, S., Ishibashi, K., Katoh, H., Kitamoto, S., Shirai, T., Tanaka, S., Kajita, M., Ishikawa, S., Yamauchi, H., Yako, Y., Kamasaki, T., Matsumoto, T., Watanabe, H., Egami, R., Sasaki, A., Nishikawa, A., Kameda, I., Maruyama, T., Narumi, R., Morita, T., Sasaki, Y., Enoki, R., Honma, S., Imamura, H., Oshima, M., Soga, T., Miyazaki, J., Duchen, M. R., Nam, J.-M., Onodera, Y., Yoshioka, S., Kikuta, J., Ishii, M., Imajo, M., Nishida, E., Fujioka, Y., Ohba, Y., Sato, T., and Fujita, Y. (2017) Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes. Nature Cell Biology, 19(5):530-541.
- Kajita M., Sugimura, K., Ohoka, A., Burden, J., Suganuma, H., Ikegawa, M., Shimada, T., Kitamura, T., Shindoh, M., Ishikawa, S., Yamamoto, S., Saitoh, S., Yako, Y., Takahashi, R., Okajima, T., Kikuta, J., Maijima, Y., Ishii, M., Tada, M., and Fujita, Y. (2014) Filamin acts as a key regulator in epithelial defence against transformed cells. Nature Communications, 5:4428.
- Hogan, C., Dupré-Crochet, S., Norman, M., Kajita, M., Zimmermann, C., Pelling, A.E., Piddini, E., Baena-López, L.A., Vincent, J. P., Hosoya, H., Itoh, Y., Pichaud, F. and Fujita, Y. (2009) Characterization of the interface between normal and transformed epithelial cells. Nature Cell Biology, 11 (4), 460-467.
Molecular OncologyProfessor: Yasuyuki Fujita
Associate Professor: Yoichiro Tamori
Assistant Professor: Nobuyuki Tanimura
Program-Specific Assistant Professor: Miho Sekai