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Oncotarget. 2013 Mar;4(3):463-73.

A kinase-independent biological activity for insulin growth factor-1 receptor (IGF-1R) : implications for inhibition of the IGF-1R signal.

Author information

1
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. fjanku@mdanderson.org

Abstract

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.

PMID:
23531874
PMCID:
PMC3717308
DOI:
10.18632/oncotarget.886
[Indexed for MEDLINE]
Free PMC Article
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