Nuclear IGF1R is a transcriptional co-activator of LEF1/TCF

Recent findings suggest that nuclear IGF1R binds to enhancer regions and functions as a transcriptional cofactor. However, the downstream transcriptional regulators of this pathway remain to be defined. Here, we show that nuclear IGF1R associates with the transcription factor LEF1 and increases promoter activity of LEF1 downstream target genes cyclin D1 and axin2 . Furthermore, nuclear IGF1R augments protein levels of cyclin D1 and axin2. Our findings suggest a novel function for IGF1R, thus further emphasizing the important role of this receptor in cancer biology. Insulin growth factor 1 receptor is known to translocate to the nucleus upon IGF1 signalling. Sehat and collaborators show in this report that nuclear IGFR1 is a transcriptional co‐factor of LEF1/TCF required for cyclin D and axin2 activation independently of β‐catenin.