Title:
Cell competition between normal and transformed epithelial cells

 

Speaker:
Yasuyuki Fujita
Affiliations: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University
Kita-ku, Kita15, Nishi7, Sapporo, 060-0815, Japan)

 

 

Abstract:
At the initial step of carcinogenesis, transformation occurs in a single cell within an epithelial sheet, and the emerging transformed cells grow while being surrounded by normal epithelial cells. However, it was not clear what happens at the boundary between normal and transformed cells. Using newly established cell culture and mouse model systems, we have shown that various phenomena can occur at the interface between normal and transformed epithelial cells [1]. For example, when Ras- or Src-transformed cells are surrounded by normal epithelial cells, various signaling pathways are activated in the transformed cells and they are often eliminated from the apical surface of the epithelial monolayer [2, 3]. These phenomena are not observed when transformed cells alone are present, suggesting that the presence of surrounding normal cells affects the signaling pathways and fate of transformed cells. Furthermore, we have demonstrated that normal epithelial cells can recognize and actively eliminate neighboring transformed cells and named this process EDAC (Epithelial Defense Against Cancer) [4].
In this seminar, I will present our recent findings and propose how this study can lead to the prevention of invasive cancer and establishment of novel types of cancer treatment: enhancing the ability of surrounding normal cells to fight against cancer cells.

 

References:
1. Maruyama, T. and Fujita, Y. Cell competition in mammals novel homeostatic machinery for embryonic development and cancer prevention. Current Opinion in Cell Biology, 15;48:106-112, 2017.
2. 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. Characterization of the interface between normal and transformed epithelial cells. Nature Cell Biology 2009; 11 (4), 460-467.
3. Kajita, M., Hogan, C., Harris, A. R., Dupre-Crochet, S., Itasaki, N., Kawakami, K., Charras, G., Tada, M., and Fujita, Y. Interaction with surrounding normal cells influences signaling pathways and behavior of Src-transformed cells. Journal of Cell Science 2010; 123 (Pt2): 171-80.
4. 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. Filamin acts as a key regulator in epithelial defence against transformed cells. Nature Communications 2015; 5:4428