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Leader cells regulate collective cell migration via Rac activation in the downstream signaling of integrin beta 1 and PI3K

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Title: Leader cells regulate collective cell migration via Rac activation in the downstream signaling of integrin beta 1 and PI3K
Authors: Yamaguchi, Naoya Browse this author
Mizutani, Takeomi Browse this author →KAKEN DB
Kawabata, Kazushige Browse this author →KAKEN DB
Haga, Hisashi Browse this author →KAKEN DB
Issue Date: 7-Jan-2015
Publisher: Nature Publishing Group
Journal Title: Scientific reports
Volume: 5
Start Page: 7656
Publisher DOI: 10.1038/srep07656
Abstract: Collective cell migration plays a crucial role in several biological processes, such as embryonic development, wound healing, and cancer metastasis. Here, we focused on collectively migrating Madin-Darby Canine Kidney (MDCK) epithelial cells that follow a leader cell on a collagen gel to clarify the mechanism of collective cell migration. First, we removed a leader cell from the migrating collective with a micromanipulator. This then caused disruption of the cohesive migration of cells that followed in movement, called "follower'' cells, which showed the importance of leader cells. Next, we observed localization of active Rac, integrin beta 1, and PI3K. These molecules were clearly localized in the leading edge of leader cells, but not in follower cells. Live cell imaging using active Rac and active PI3K indicators was performed to elucidate the relationship between Rac, integrin beta 1, and PI3K. Finally, we demonstrated that the inhibition of these molecules resulted in the disruption of collective migration. Our findings not only demonstrated the significance of a leader cell in collective cell migration, but also showed that Rac, integrin beta 1, and PI3K are upregulated in leader cells and drive collective cell migration.
Rights: http://creativecommons.org/licenses/by-nc-sa/4.0/
Type: article
URI: http://hdl.handle.net/2115/58058
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 芳賀 永

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