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Rab5c promotes AMAP1-PRKD2 complex formation to enhance β1 integrin recycling in EGF-induced cancer invasion

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Title: Rab5c promotes AMAP1-PRKD2 complex formation to enhance β1 integrin recycling in EGF-induced cancer invasion
Authors: Onodera, Yasuhito Browse this author
Nam, Jin-Min Browse this author
Hashimoto, Ari Browse this author →KAKEN DB
Norman, Jim C. Browse this author
Shirato, Hiroki Browse this author →KAKEN DB
Hashimoto, Shigeru Browse this author →KAKEN DB
Sabe, Hisataka Browse this author →KAKEN DB
Issue Date: 25-Jun-2012
Publisher: Rockefeller University Press
Journal Title: Journal of Cell Biology: JCB
Volume: 197
Issue: 7
Start Page: 983
End Page: 996
Publisher DOI: 10.1083/jcb.201201065
Abstract: Epidermal growth factor receptor (EGFR) signaling is one of the crucial factors in breast cancer malignancy. Breast cancer cells often overexpress Arf6 and its effector, AMAP1/ASAP1/DDEF1; in these cells, EGFR signaling may activate the Arf6 pathway to induce invasion and metastasis. Active recycling of some integrins is crucial for invasion and metastasis. Here, we show that the Arf6-AMAP1 pathway links to the machinery that recycles β1 integrins, such as α3β1, to promote cell invasion upon EGFR stimulation. We found that AMAP1 had the ability to bind directly to PRKD2 and hence to make a complex with the cytoplasmic tail of the β1 subunit. Moreover, GTP-Rab5c also bound to AMAP1, and activation of Rab5c by EGFR signaling was necessary to promote the intracellular association of AMAP1 and PRKD2. Our results suggest a novel mechanism by which EGFR signaling promotes the invasiveness of some breast cancer cells via integrin recycling.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 佐邊 壽孝

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