The arginine methyltransferase PRMT1 regulates IGF-1 signaling in breast cancer.

摘要: Aside from its well-known nuclear routes of signaling, estrogen also mediates effects through cytoplasmic signaling. Estrogen signaling involves numerous posttranslational modifications receptor ERα, the best known being phosphorylation. Our research group previously showed that upon stimulation, ERα is methylated on residue R260 and forms mERα/Src/PI3K complex, central to rapid transduction nongenomic signals. Regulation via phosphorylation by growth factors well recognized, we wondered whether they could trigger methylation (mERα). Here, found IGF-1 treatment MCF-7 cells induced arginine methyltransferase PRMT1 triggered binding mERα IGF-1R. Mechanistically, bound constitutively IGF-1R became activated stimulation. Moreover, expression or pharmacological inhibition impaired findings were substantiated in a cohort breast tumors which was positively correlated with ERα/Src ERα/PI3K expression, hallmarks reinforcing link between mERα. Altogether, these results provide new insight into interference, open novel perspectives for combining endocrine therapies inhibitors ERα-positive tumors.