Publication Date:
2016-07-19
Description:
Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro-environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target of rapamycin complex 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies. We propose that in glioblastoma, and possibly other cancers, abundant glucose or acetate, which are readily available to tumor cells in their native environment, facilitate biochemical modification of a core component of the growth factor receptor signaling pathway, mTOR complex 2, driving growth and rendering tumors resistant to drugs that target upstream components of growth factor signaling pathways.
Print ISSN:
0265-9247
Electronic ISSN:
1521-1878
Topics:
Biology
,
Medicine
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