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 results in decreased intracellular glucose levels, whereas treatment with the 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.
Original language | English (US) |
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Pages (from-to) | 463-473 |
Number of pages | 11 |
Journal | Oncotarget |
Volume | 4 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2013 |
Keywords
- Autophagy
- IGF-1R
- Intracellular glucose
- MCF7 cells
- OSI-906
ASJC Scopus subject areas
- Oncology