TY - JOUR
T1 - miR-181 elevates Akt signaling by co-targeting PHLPP2 and INPP4B phosphatases in luminal breast cancer
AU - Strotbek, Michaela
AU - Schmid, Simone
AU - Sánchez-González, Ismael
AU - Boerries, Melanie
AU - Busch, Hauke
AU - Olayioye, Monilola A.
PY - 2017/5/15
Y1 - 2017/5/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85015207549&partnerID=8YFLogxK
U2 - 10.1002/ijc.30661
DO - 10.1002/ijc.30661
M3 - Journal articles
C2 - 28224609
AN - SCOPUS:85015207549
VL - 140
SP - 2310
EP - 2320
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 10
ER -