title: Egr-1 activation by cancer-derived extracellular vesicles promotes endothelial cell migration via ERK1/2 and JNK signaling pathways.
abstract: Various mammalian cells, including cancer cells, shed extracellular vesicles (EVs), also known as exosomes and microvesicles, into surrounding tissues. These EVs play roles in tumor growth and metastasis by promoting angiogenesis. However, the detailed mechanism of how cancer-derived EVs elicit endothelial cell activation remains unknown. Here, we provide evidence that early growth response-1 (Egr-1) activation in endothelial cells is involved in the angiogenic activity of colorectal cancer cell-derived EVs. Both RNA interference-mediated downregulation of Egr-1 and ERK1/2 or JNK inhibitor significantly blocked EV-mediated Egr-1 activation and endothelial cell migration. Furthermore, lipid raft-mediated endocytosis inhibitor effectively blocked endothelial Egr-1 activation and migration induced by cancer-derived EVs. Our results suggest that Egr-1 activation in endothelial cells may be a key mechanism involved in the angiogenic activity of cancer-derived EVs. These findings will improve our understanding regarding the proangiogenic activities of EVs in diverse pathological conditions including cancer, cardiovascular diseases, and neurodegenerative diseases.
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Yae Jin
authors.initials: YJ
authors.lastname: Yoon
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Dae-Kyum
authors.initials: DK
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Chang Min
authors.initials: CM
authors.lastname: Yoon
authors.affiliation: Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Jaesung
authors.initials: J
authors.lastname: Park
authors.affiliation: Ewha Institute of Convergence Medicine, Ewha Womans University Medical Center, Seoul 158-710, Republic of Korea.
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Roh
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D000067128:Extracellular Vesicles / Q000378:metabolism*; D045325:HCT116 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D021962:Membrane Microdomains / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D034622:RNA Interference
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1