A kinase-independent biological activity for insulin growth factor-1 receptor (IGF-1R) : implications for inhibition of the IGF-1R signal. Oncotarget 2013 Mar;4(3):463-73
Date
03/28/2013Pubmed ID
23531874Pubmed Central ID
PMC3717308DOI
10.18632/oncotarget.886Scopus ID
2-s2.0-84879020294 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
It has been demonstrated that epidermal growth factor receptor (EGFR) can have kinase independent activity. EGFR kinase-independent function maintains intracellular glucose levels via sodium glucose transporter protein 1 (SGLT1) and supports cell survival. It is plausible that this phenomenon can apply to other receptor tyrosine kinases. We found that transfection of insulin-like growth factor receptor (IGF-1R) siRNA into HEK293 (human embryonic kidney) and MCF7 (metastatic breast cancer) cells result in decreased intracellular glucose levels, whereas treatment with an IGF-1R tyrosine kinase inhibitor OSI-906 did not affect intracellular glucose levels. In addition, IGF-1R interacted with SGLT1 in a manner similar to that previously reported with EGFR. The combination of IGF-1R siRNA and OSI-906 resulted in decreased viability of HEK293 and MCF7 cell lines compared to either agent alone. Collectively, these experiments suggest that IGF-1R, has kinase-independent biologic functions and provide a rationale for combining anti-IGF-1R antibodies or siRNA and IGF-1R small molecule inhibitors.
Author List
Janku F, Huang HJ, Angelo LS, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ApoptosisBlotting, Western
Cell Cycle
Cell Survival
Flow Cytometry
Glucose
HEK293 Cells
Humans
Imidazoles
Intracellular Space
MCF-7 Cells
Pyrazines
RNA Interference
Receptor, IGF Type 1
Signal Transduction
Sodium-Glucose Transporter 1