miR-181 elevates Akt signaling by co-targeting PHLPP2 and INPP4B phosphatases in luminal breast cancer

Michaela Strotbek, Simone Schmid, Ismael Sánchez-González, Melanie Boerries, Hauke Busch, Monilola A. Olayioye*

*Corresponding author for this work
5 Citations (Scopus)

Abstract

The PI3K-Akt pathway is one of the most commonly dysregulated cancer-associated signaling pathways. Here we report an oncogenic function for the miR-181 family in luminal breast cancer cells that involves Akt hyperactivation. We show that miR-181a and miR-181d posttranscriptionally suppress the expression of PHLPP2 and INPP4B phosphatases, resulting in elevated growth factor-induced Akt phosphorylation. Ectopic expression of miR-181a and miR-181d promoted S-phase entry and cell proliferation, which was reversed by pharmacological Akt inhibition. Importantly, the expression of miR-181 family members and PHLPP2/INPP2B are inversely correlated in primary human estrogen receptor-positive breast cancers, supporting the clinical relevance of our findings.

Original languageEnglish
JournalInternational Journal of Cancer
Volume140
Issue number10
Pages (from-to)2310-2320
Number of pages11
ISSN0020-7136
DOIs
Publication statusPublished - 15.05.2017

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