ERG function in prostate cells is regulated by distinct positive feedback loops depending on AKT signaling status

Expression of ERG in prostate cells can promote either luminal epithelial or mesenchymal cell fates depending on the status of the PI3K/AKT signaling pathway. Phosphorylation of ERG by ERK is important for oncogenic activity and can be regulated by the TLR4 signaling pathway.

Here we found that the TLR4 pathway regulated ERG phosphorylation when AKT signaling was low, but the VEGF pathway promoted ERG phosphorylation when AKT signaling was high. Inhibition of the PI3K/AKT pathway in ERG-positive prostate cells resulted in loss of androgen receptor expression, gain of mesenchymal markers and loss of sensitivity to androgen receptor inhibition.