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 language | English |
|---|---|
| Journal | International Journal of Cancer |
| Volume | 140 |
| Issue number | 10 |
| Pages (from-to) | 2310-2320 |
| Number of pages | 11 |
| ISSN | 0020-7136 |
| DOIs | |
| Publication status | Published - 15.05.2017 |
Funding
We thank Lisa Pieper for assisting with figure assembly and statistical evaluation of the data. MAO is funded by the Heisenberg program of the Deutsche Forschungsgemeinschaft (DFG). HB and MB are supported by the DFG via the Collaborative Research Centre 850, by the DFG grant InKoMBio: SPP 1395 and MB is funded by the German Federal Ministry of Education and Research within the framework of the e:Med research and funding concept DeCaRe (FKZ 01ZX1409B).
