4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors Journal Article
| Authors: | She, Q. B.; Halilovic, E.; Ye, Q.; Zhen, W.; Shirasawa, S.; Sasazuki, T.; Solit, D. B.; Rosen, N. |
| Article Title: | 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors |
| Abstract: | PIK3CA and PTEN alterations are common in human cancer, but only a fraction of such tumors are dependent upon AKT signaling. AKT independence is associated with redundant activation of cap-dependent translation mediated by convergent regulation of the translational repressor 4E-BP1 by the AKT and ERK pathways. This provides mechanistic bases for the limited activity of AKT and MEK inhibitors in tumors with comutation of both pathways and the profound synergy observed with combined inhibition. Whereas such tumors are sensitive to a dominant active 4E-BP1 mutant, knockdown of 4E-BP1 expression reduces their dependence on AKT/ERK signaling for translation or survival. Thus, 4E-BP1 plays a prominent role in mediating the effects of these pathways in tumors in which they are activated by mutation. © 2010 Elsevier Inc. |
| Keywords: | signal transduction; mitogen activated protein kinase; protein kinase b; cancer survival; protein expression; survival rate; unclassified drug; gene mutation; human cell; gene deletion; mutation; protein function; cell proliferation; animals; mice; apoptosis; enzyme inhibition; colonic neoplasms; rna, small interfering; enzyme activation; tumor cells, cultured; phosphatidylinositol 3 kinase; cancer inhibition; blotting, western; mice, nude; reverse transcriptase polymerase chain reaction; rna, messenger; 1-phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; pten phosphohydrolase; tumor cell; initiation factor 4e binding protein 1; adaptor proteins, signal transducing; extracellular signal-regulated map kinases; phosphoproteins; protein biosynthesis; ras protein; k ras protein; phosphoinositide 3 kinase catalytic subunit alpha |
| Journal Title: | Cancer Cell |
| Volume: | 18 |
| Issue: | 1 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2010-07-01 |
| Start Page: | 39 |
| End Page: | 51 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2010.05.023 |
| PUBMED: | 20609351 |
| PROVIDER: | scopus |
| PMCID: | PMC3286650 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 20 April 2011" - "CODEN: CCAEC" - "Source: Scopus" |
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