7/25, LSBM Monday Seminar Series #19, Shunsuke Kon, Autophagic perturbation caused by reduced lysosomal activity is indispensable for cell competition

Presenter: Shunsuke Kon
Affiliation: Tokyo University of Science, Organization for Research Advancement, Research Institute for Biomedical Sciences, Research Division
Date: July 25th




Autophagic perturbation caused by reduced lysosomal activity is indispensable for cell competition



Cell competition is a process by which unwanted cells are eliminated from tissues. Apical extrusion is one mode whereby normal epithelial cells remove transformed cells, but it remains unkown how this process is mechanically effected. In this study, we show that autophagic flux is attenuated in RasV12-transformed cells surrounded by normal cells due to lysosomal dysfunction, and that chemical manipulation of lysosomal activity compromises apical extrusion of RasV12 cells. We further find that RasV12 cells deficient in autophagy initiation machinery are resistant to elimination pressure exerted by normal cells, suggesting that autophagosome formation is required for cell competition. Analysis of a mouse model of cell competition revealed that autophagy-ablated RasV12 cells are less readily eliminated by cell competition, and remaining transformed cells destroy ductal integrity, leading to chronic pancreatitis. Collectively, these results illuminate a positive role of autophagy in cell competition and reveal a homeostasis-preserving function of autophagy upon emergence of transformed cells.



  • Akter, E., Tasaki, Y., Nakai, K., Hachiya, K., Lin, H., Konno, M., Umeda, Y., Yamano, S., Fujita, Y. and Kon, S. Autophagic perturbation caused by reduced lysosomal activity is indispensable for cell competition. Cell Reports, In press.
  • Watanabe, H., Ishibashi, K., Mano, H., Kitamoto, S., Sato, N., Hoshiba, K., Kato, M., Matsuzawa, F., Takeuchi, Y., Shirai, T., Ishikawa, S., Morioka, Y., Imagawa, T., Sakaguchi, K., Yonezawa, S., Kon, S♯. and Fujita, Y♯. Mutant p53-expressing cells undergo necroptosis via cell competition with the neighboring normal epithelial cells. ♯同等責任著者 Cell Reports, 23, 3721-3729, 2018
  • 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. : Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes. Nature Cell Biology, 19, 530-541, 2017




1998年3月 愛媛県立松山東高校 卒業

2003年3月 東北大学工学部化学バイオ科 卒業

2008年3月 東北大学生命科学研究科 博士後期課程 修了 (佐竹 正延 教授)

2008年4月 東北大学加齢医学研究所 博士研究員 (佐竹 正延 教授)

2009年4月 東北大学加齢医学研究所 助教 (佐竹 正延 教授)

2013年7月 北海道大学遺伝子病制御研究所 助教 (藤田 恭之 教授)

2017年7月 北海道大学遺伝子病制御研究所 講師 (藤田 恭之 教授)

2018年4月 東京理科大学生命医科学研究所 独立講師