Oncotarget

Research Papers:

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

Filip Janku _, Helen J. Huang, Laura S. Angelo and Razelle Kurzrock

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Oncotarget. 2012; 4:463-473. https://doi.org/10.18632/oncotarget.886

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Abstract

Filip Janku1, Helen J. Huang1, Laura S. Angelo1, and Razelle Kurzrock2

1 Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas

2 Moores Cancer Center, The University of California San Diego, La Jolla, California

Correspondence:

Filip Janku, email:

Keywords: IGF-1R, OSI-906, intracellular glucose, autophagy, MCF7 cells

Received: February 17, 2013 Accepted: March 23, 2013 Published: March 23, 2013

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.


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