title: The EGF receptor interacts with the type 1 IGF receptor and regulates its stability.
abstract: 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.
authors.affiliation: Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Johann
authors.initials: J
authors.lastname: Riedemann
authors.forename: Megumi
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Muhammad
authors.initials: M
authors.lastname: Sohail
authors.forename: Valentine M
authors.initials: VM
authors.lastname: Macaulay
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D019281:Dimerization; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D034741:RNA, Small Interfering / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D025801:Ubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D061988:Proteasome Inhibitors; D034741:RNA, Small Interfering; D025801:Ubiquitin; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D046988:Proteasome Endopeptidase Complex