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Both the epidermal growth factor receptor (EGFR) 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 EGFR hyper-phosphorylation 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 IGF1R and EGFR when overexpressed in SKUT-1 cells, and between endogenous IGF1R and EGFR 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 EGFR knockdown also suppressed IGF1R protein levels. Further investigation revealed that EGFR 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 IGF1R protein.

Original publication

DOI

10.1016/j.bbrc.2007.02.012

Type

Journal article

Journal

Biochem Biophys Res Commun

Publication Date

13/04/2007

Volume

355

Pages

707 - 714

Keywords

Breast Neoplasms, Cell Line, Tumor, Dimerization, ErbB Receptors, Humans, Proteasome Endopeptidase Complex, Proteasome Inhibitors, RNA, Small Interfering, Receptor, IGF Type 1, Ubiquitin