| Title: | GEP100-Arf6-AMAP1-Cortactin Pathway Frequently Used in Cancer Invasion Is Activated by VEGFR2 to Promote Angiogenesis |
| Authors: | Hashimoto, Ari Browse this author |
| Hashimoto, Shigeru Browse this author |
| Ando, Ryo Browse this author |
| Noda, Kosuke Browse this author |
| Ogawa, Eiji Browse this author |
| Kotani, Hirokazu Browse this author |
| Hirose, Mayumi Browse this author |
| Menju, Toshi Browse this author |
| Morishige, Masaki Browse this author |
| Manabe, Toshiaki Browse this author |
| Toda, Yoshinobu Browse this author |
| Ishida, Susumu Browse this author |
| Sabe, Hisataka Browse this author →KAKEN DB |
| Issue Date: | 15-Aug-2011 |
| Publisher: | Public Library of Science |
| Journal Title: | PLoS One |
| Volume: | 6 |
| Issue: | 8 |
| Start Page: | e23359 |
| Publisher DOI: | 10.1371/journal.pone.0023359 |
| Abstract: | Angiogenesis and cancer invasiveness greatly contribute to cancer malignancy. Arf6 and its effector, AMAP1, are frequently overexpressed in breast cancer, and constitute a central pathway to induce the invasion and metastasis. In this pathway, Arf6 is activated by EGFR via GEP100. Arf6 is highly expressed also in human umbilical vein endothelial cells (HUVECs) and is implicated in angiogenesis. Here, we found that HUVECs also highly express AMAP1, and that vascular endothelial growth factor receptor-2 (VEGFR2) recruits GEP100 to activate Arf6. AMAP1 functions by binding to cortactin in cancer invasion and metastasis. We demonstrate that the same GEP100-Arf6-AMAP1-cortactin pathway is essential for angiogenesis activities, including cell migration and tubular formation, as well as for the enhancement of cell permeability and VE-cadherin endocytosis of VEGF-stimulated HUVECs. Components of this pathway are highly expressed in pathologic angiogenesis, and blocking of this pathway effectively inhibits VEGF- or tumor-induced angiogenesis and choroidal neovascularization. The GEP100-Arf6-AMAP1-cortactin pathway, activated by receptor tyrosine kinases, appears to be common in angiogenesis and cancer invasion and metastasis, and provides their new therapeutic targets. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/47068 |
| 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)
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