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mTORC2 activity in brain cancer: Extracellular nutrients are required to maintain oncogenic signaling
Kenta Masui1, Noriyuki Shibata1, Webster K Cavenee2
1Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan.
Abstract:
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.
Insights
External nutrients fuel glioblastoma (GBM) growth and drug resistance by sustaining mechanistic target of rapamycin complex 2 (mTORC2) signaling. This suggests metabolism influences oncogenic signaling and treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metabolism
Background:
- Growth factor receptor signaling mutations drive glioblastoma (GBM) growth by altering nutrient metabolism.
- The influence of micro-environmental nutrient availability on oncogenic signaling and drug resistance in GBM remains unclear.
Purpose of the Study:
- To investigate how external nutrient levels impact GBM growth, oncogenic signaling, and treatment resistance.
- To test the hypothesis that nutrients maintain mechanistic target of rapamycin complex 2 (mTORC2) activity in GBM.
Main Methods:
- The study likely involved experiments examining GBM cell lines or models under varying nutrient conditions.
- Assays were probably used to measure mTORC2 activity, tumor growth, and response to therapies.
Main Results:
- External nutrients were found to promote GBM growth and treatment resistance.
- Nutrient availability appears to maintain the activity of mTORC2, a key signaling intermediate.
Conclusions:
- Altered cellular metabolism is not just a consequence of oncogenic signaling but can also determine its activity in GBM.
- Systemic metabolic status may influence patient response to targeted cancer therapies for glioblastoma.
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