title: Dab2 is pivotal for endothelial cell migration by mediating VEGF expression in cancer cells.
abstract: Although angiogenesis is crucial for tumor growth and metastasis, the molecular mechanisms controlling this process are not clearly understood. Here, we explore the role of Dab2 in tumor angiogenesis. We found that Dab2 is expressed in several cancer cells, including A549 lung cancer cells, but it is hardly detectable in SW480 colon cancer cells. Migration and Erk phosphorylation were enhanced in human umbilical vein endothelial cells (HUVECs) treated with the conditioned medium obtained from Dab2-overexpressing SW480 stable cells. In addition, vascular endothelial growth factor (VEGF) protein was strongly detected in conditioned medium derived from Dab2-overexpressing SW480 cells, and Erk phosphorylation enhanced by Dab2(+) CM was restored by VEGF inhibition. Moreover, Dab2 depletion in A549 cells led to a decrease in HUVEC migration and Erk phosphorylation. Furthermore, we show that Dab2 is required for the TGFβ-induced gene expression of angiogenic factors such as VEGF and FGF2. Taken together, these results suggest that Dab2, which is expressed in cancer cells, is pivotal for endothelial cell migration by affecting VEGF expression.
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk, 790-784, Republic of Korea.
authors.forename: Seong-Moon
authors.initials: SM
authors.lastname: Cheong
authors.forename: Hyemin
authors.initials: H
authors.lastname: Choi
authors.forename: Bok Sil
authors.initials: BS
authors.lastname: Hong
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.forename: Jin-Kwan
authors.initials: JK
authors.lastname: Han
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010766:Phosphorylation; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D017077:Culture Media, Conditioned; C102885:DAB2 protein, human; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D048049:Extracellular Signal-Regulated MAP Kinases