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タイトル: | Competition for Space Is Controlled by Apoptosis-Induced Change of Local Epithelial Topology |
著者: | Tsuboi, Alice Ohsawa, Shizue Umetsu, Daiki Sando, Yukari Kuranaga, Erina Igaki, Tatsushi Fujimoto, Koichi |
著者名の別形: | 大澤, 志津江 山銅, ゆかり 井垣, 達吏 |
キーワード: | cell competition tissue mechanics cell intercalation cell packing tumor progression differential growth vertex model epithelial tissue Hippo Ras |
発行日: | 9-Jul-2018 |
出版者: | Elsevier BV |
誌名: | Current Biology |
巻: | 28 |
号: | 13 |
開始ページ: | 2115 |
終了ページ: | 2128 |
抄録: | During the initial stage of tumor progression, oncogenic cells spread despite spatial confinement imposed by surrounding normal tissue. This spread of oncogenic cells (winners) is thought to be governed by selective killing of surrounding normal cells (losers) through a phenomenon called “cell competition” (i.e., supercompetition). Although the mechanisms underlying loser elimination are increasingly apparent, it is not clear how winner cells selectively occupy the space made available following loser apoptosis. Here, we combined live imaging analyses of two different oncogenic clones (Yki/YAP activation and Ras activation) in the Drosophila epithelium with computer simulation of tissue mechanics to elucidate such a mechanism. Contrary to the previous expectation that cell volume loss after apoptosis of loser cells was simply compensated for by the faster proliferation of winner cells, we found that the lost volume was compensated for by rapid cell expansion of winners. Mechanistically, the rapid winner-dominated cell expansion was driven by apoptosis-induced epithelial junction remodeling, which causes re-connection of local cellular connectivity (cell topology) in a manner that selectively increases winner apical surface area. In silico experiments further confirmed that repetition of loser elimination accelerates tissue-scale winner expansion through topological changes over time. Our proposed mechanism for linking loser death and winner expansion provides a new perspective on how tissue homeostasis disruption can initiate from an oncogenic mutation. |
著作権等: | © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
URI: | http://hdl.handle.net/2433/232695 |
DOI(出版社版): | 10.1016/j.cub.2018.05.029 |
PubMed ID: | 29910075 |
出現コレクション: | 学術雑誌掲載論文等 |
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