| First Author | Hsieh AC | Year | 2010 |
| Journal | Cancer Cell | Volume | 17 |
| Issue | 3 | Pages | 249-61 |
| PubMed ID | 20227039 | Mgi Jnum | J:158661 |
| Mgi Id | MGI:4439408 | Doi | 10.1016/j.ccr.2010.01.021 |
| Citation | Hsieh AC, et al. (2010) Genetic dissection of the oncogenic mTOR pathway reveals druggable addiction to translational control via 4EBP-eIF4E. Cancer Cell 17(3):249-61 |
| abstractText | We genetically dissect the contribution of the most prominent downstream translational components of mTOR signaling toward Akt-driven lymphomagenesis. While phosphorylation of rpS6 is dispensable for cancer formation, 4EBP-eIF4E exerts significant control over cap-dependent translation, cell growth, cancer initiation, and progression. This effect is mediated at least in part through 4EBP-dependent control of Mcl-1 expression, a key antiapoptotic protein. By using an active site inhibitor of mTOR, PP242, we show a marked therapeutic response in rapamycin-resistant tumors. The therapeutic benefit of PP242 is mediated through inhibition of mTORC1-dependent 4EBP-eIF4E hyperactivation. Thus, the 4EBP-eIF4E axis downstream of mTOR is a druggable mediator of translational control and Akt-mediated tumorigenesis that has important implications for the treatment of human cancers. |
