The inflammatory prostaglandin E-2 (PGE(2)) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE(2) directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE(2)-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE(2) increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE(2) EP4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE(2) increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE(2)-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE(2) increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE(2) mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth. (C) 2014 Elsevier Inc. All rights reserved.