The EGF receptor interacts with the type 1 IGF receptor and regulates its stability

Both the epidermal growth factor receptor (EGER) and type 1 insulin-like growth factor receptor (IGF1R) require homo- and hetero-dimerisation with their own family members to acquire full function. We recently showed that IGF1R gene silencing led to EGER hyperphosphorylation in human breast cancer cells, and hypothesised that this crosstalk might be associated with direct IGF1R:EGFR interaction. Indeed we could detect reciprocal co-precipitation between the IGF I R and EGER when overexpressed in SKUT-1 cells, and between endogenous IGH1R and EGER in MDA-MB-468 breast carcinoma cells, two squamous cancer cell lines, and clinical samples of breast cancer. Interaction was abolished by knockdown of either receptor, and we noted that EGER knockdown also suppressed IGF1R protein levels. Further investigation revealed that EGER depletion induced enhancement of IGF1R ubiquitylation and degradation. These results indicate novel evidence of crosstalk between two key cancer treatment targets, capable of modifying the stability of IGF I R protein. (c) 2007 Elsevier Inc. All rights reserved.