Targeted disruption of β-arrestin 2-mediated signaling pathways by aptamer chimeras leads to inhibition of leukemic cell growth.

Published online

Journal Article

UNLABELLED: β-arrestins, ubiquitous cellular scaffolding proteins that act as signaling mediators of numerous critical cellular pathways, are attractive therapeutic targets because they promote tumorigenesis in several tumor models. However, targeting scaffolding proteins with traditional small molecule drugs has been challenging. Inhibition of β-arrestin 2 with a novel aptamer impedes multiple oncogenic signaling pathways simultaneously. Additionally, delivery of the β-arrestin 2-targeting aptamer into leukemia cells through coupling to a recently described cancer cell-specific delivery aptamer, inhibits multiple β-arrestin-mediated signaling pathways known to be required for chronic myelogenous leukemia (CML) disease progression, and impairs tumorigenic growth in CML patient samples. The ability to target scaffolding proteins such as β-arrestin 2 with RNA aptamers may prove beneficial as a therapeutic strategy. HIGHLIGHTS: An RNA aptamer inhibits β-arrestin 2 activity.Inhibiting β-arrestin 2 impedes multiple tumorigenic pathways simultaneously.The therapeutic aptamer is delivered to cancer cells using a cell-specific DNA aptamer.Targeting β-arrestin 2 inhibits tumor progression in CML models and patient samples.

Full Text

Duke Authors

Cited Authors

  • Kotula, JW; Sun, J; Li, M; Pratico, ED; Fereshteh, MP; Ahrens, DP; Sullenger, BA; Kovacs, JJ

Published Date

  • 2014

Published In

Volume / Issue

  • 9 / 4

Start / End Page

  • e93441 -

PubMed ID

  • 24736311

Pubmed Central ID

  • 24736311

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0093441

Language

  • eng

Conference Location

  • United States