Small molecule inhibition of ERK dimerization prevents tumorigenesis by Ras-ERK pathway oncogenes

ABSTRACT: About 50% of human malignancies exhibit unregulated signalling through the Ras-ERK1/2 (ERK) pathway, as a consequence of activating mutations in members of Ras and Raf families. However, the quest for alternative Ras-ERK pathway-directed therapies is desirable. Upon phosphorylation ERK dimerize. We had previously demonstrated that dimerization is essential for ERK extranuclear but not nuclear signaling. Furthermore, by molecular biology approaches, we showed that specifically inhibiting ERK extranuclear component, by impeding ERK dimerization, is sufficient for curtailing tumor progression. Here, we have identified a small molecule inhibitor for ERK dimerization in vitro and in vivo that, without affecting ERK phosphorylation, prevents tumorigenesis driven by Ras-ERK pathway oncogenes, bot

ORGANISM(S): Homo sapiens

SUBMITTER: Piero Crespo 

PROVIDER: E-GEOD-68230 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress