Nontoxic chemical interdiction of the epithelial-to-mesenchymal transition by targeting cap-dependent translation.

ABSTRACT: Normal growth and development depends upon high fidelity regulation of cap-dependent translation initiation, a process that is usurped and redirected in cancer to mediate acquisition of malignant properties. The epithelial-to-mesenchymal transition (EMT) is a key translationally regulated step in the development of epithelial cancers and pathological tissue fibrosis. To date, no compounds targeting EMT have been developed. Here we report the synthesis of a novel class of histidine triad nucleotide binding protein (HINT)-dependent pronucleotides that interdict EMT by negatively regulating the association of eIF4E with the mRNA cap. Compound eIF4E inhibitor-1 potently inhibited cap-dependent translation in a dose-dependent manner in zebrafish embryos without causing developmental abnormaliti

SUBMITTER: Ghosh B 

PROVIDER: S-EPMC2796976 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature