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- W2056562253 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCEphB4 is a member of the Eph RTK family. Its classical role has been shown to act in neuronal guidance and mediate venal/arterial separation. In contrast to these more established roles, EphB4's function in cancer is controversial since both tumor promoting as well as tumor suppressing functions have been ascribed to it. Here we provide a vivid illustration of this intriguing dichotomy by showing that EphB4 activation resulted in inhibition of the Ras/ERK pathway in endothelial cells but induction of the same pathway in MCF-7 breast cancer cells. This was true if EphB4 was stimulated with ephrinB2, its natural ligand, or an EphB4-specific fully human monoclonal antibody. The reason for these dramatic differences is due to potential functional coupling of EphB4 to different downstream effectors. In HUVEC cells, the RNAi knockdown of p120 RasGAP, a Ras inhibitor, abrogated the inhibitory effect on Ras/ERK pathway. However, in MCF7 cells, RNAi knockdown of PP2A, which has been shown to activate the Ras/ERK pathway through removal of the inhibitory phosphorylation on c-Raf, negated EphB4-driven activation of the Ras/ERK pathway. This represents the first time a functional coupling between Eph receptor and PP2A has been established, and this interaction appears to confer activation but not suppression of an oncogenic pathway. Our study also demonstrates the caveats and potential challenges of targeting EphB4 for cancer therapy due to the presumed conflicting effects on cancer cell and endothelial cell compartments.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 307." @default.
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- W2056562253 date "2010-04-15" @default.
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- W2056562253 title "Abstract 307: EphB4 promotes or suppresses Ras/ERK pathway depending on cellular contexts: Implications for EphB4 as a cancer target" @default.
- W2056562253 doi "https://doi.org/10.1158/1538-7445.am10-307" @default.
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