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Fig. 4.
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Discussion
PGE2 regulates tumor angiogenesis by in part promoting EC survival and by increasing EC migration. The signaling ABT-263 implicated in these processes have however not been fully characterized. In this study, we have analyzed the role of mTORC1 and mTORC2 in PGE2-mediated EC responses. Our findings were that PGE2 activates both complexes in EC and that mTORC2 is an important signaling intermediary in PGE2-mediated EC survival and migration.
Two reports have demonstrated that both EP2 and EP4 receptors regulate PGE2-mediated EC motility [7] and [8]. In both studies, Erk activation was necessary for EP2 and EP4-mediated EC migration. Consistent with these observations, we also observed that the inhibition of the Mek/Erk pathway inhibited PGE2-induced EC migration (data not shown). Interestingly, a recent study has described a link between mTORC2 and Erk. In EC, MHC class I and integrin induced Erk activation was mediated by mTORC2 [25]. However, this effect was selective for MHC class I and integrin as growth factor mediated Erk activation was not dependent on mTORC2 [25]. We observed that inhibition of mTORC2 in EC did not block PGE2-mediated Erk activation (data not shown) suggesting that Erk and mTORC2 act through two different pathways to regulate PGE2-induced EC migration.