Gene interactions and pathways from curated databases and text-mining
Oncogene 2009, PMID: 19597469

Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells.

Dai, J; Peng, L; Fan, K; Wang, H; Wei, R; Ji, G; Cai, J; Lu, B; Li, B; Zhang, D; Kang, Y; Tan, M; Qian, W; Guo, Y

Angiogenesis is a key step in tumor growth and metastasis. The mechanism by which osteopontin (OPN) induces the angiogenesis of endothelial cells remains unclear. Here, we show that OPN confers cytoprotection through the activation of the PI3K/Akt pathway with subsequent upregulation of Bcl-xL and activation of nuclear factor-kappaB. OPN enhances the expression of vascular endothelial growth factor (VEGF) through the phosphorylation of AKT and extracellular signal-regulated kinase (ERK). In turn, OPN-induced VEGF activates PI3K/AKT and the ERK1/2 pathway as a positive feedback signal. Blocking the feedback signal by anti-VEGF antibody, PI3-kinase inhibitor or ERK inhibitor can partially inhibit the OPN-induced human umbilical vein endothelial cell (HUVEC) motility, proliferation and tube formation, while blocking the signal by anti-OPN or anti-alphavbeta3 antibody completely abrogates the biological effects of OPN on HUVECs. In addition, blood vessel formation is also investigated in vivo. The antiangiogenesis efficacy of anti-OPN antibody in vivo is more effective than that of anti-VEGF antibody, which only blocks the feedback signals. These data show that OPN enhances angiogenesis directly through PI3K/AKT- and ERK-mediated pathways with VEGF acting as a positive feedback signal. The results suggest that OPN might be a valuable target for developing novel antiangiogenesis therapy for treatment of cancer.

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Text Mining Data

ERK1/2 → Osteopontin: " Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells "

PI3K/AKT → Osteopontin: " Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells "

PI3K/AKT → Osteopontin: " Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells "

vascular endothelial growth factor → OPN: " OPN enhances the expression of vascular endothelial growth factor ( VEGF ) through the phosphorylation of AKT and extracellular signal regulated kinase ( ERK ) "

VEGF → OPN: " In turn, OPN induced VEGF activates PI3K/AKT and the ERK1/2 pathway as a positive feedback signal "

PI3K/AKT → VEGF: " In turn, OPN induced VEGF activates PI3K/AKT and the ERK1/2 pathway as a positive feedback signal "

PI3K/AKT → VEGF: " In turn, OPN induced VEGF activates PI3K/AKT and the ERK1/2 pathway as a positive feedback signal "

Manually curated Databases

No curated data.