The Regulation of Cell Metabolism and Proliferation by mTOR complex 2

Project Details

Description

DESCRIPTION (provided by applicant): Aberrant cellular metabolism has emerged as a hallmark of cancer. In highly proliferating cells including cancer cells, glucose metabolism is diverted from energy (ATP) production to the glycolytic and biosynthetic pathways to enable de novo synthesis of nucleotides, membrane and protein components required for cell proliferation. Signal transduction pathways triggered by growth factor receptors play a role in the metabolic switch. For example, enhanced PI3K/Akt signaling can upregulate glucose uptake and flux through glycolysis. Reciprocally, metabolic intermediates and enzymes could impinge on signaling molecules as well. How this bidirectional regulation can be orchestrated to promote cellular proliferation is poorly understood. Identifying critical signaling molecules that couple metabolism with cell proliferation would provide insights for development of new therapeutic targets not only for cancer but other diseases that are impacted by high cellular proliferation rates and defective metabolism such as diabetes and autoimmune disorders. Our proposed studies will examine how mTORC2 can serve as a switch that links the metabolic biosynthetic pathway to cellular proliferation. Our studies will uncover novel insights on the significance of the Warburg effect (enhanced aerobic glycolysis) on tumorigenesis and how a key signaling molecule (mTOR) can control the metabolic biosynthetic pathway to promote proliferation. Our findings will have direct implications for the development of novel therapeutic targets for diseases impacted by high proliferation and altered metabolism such as cancer, diabetes, and autoimmune disorders.
StatusFinished
Effective start/end date4/1/086/30/19

Funding

  • National Institute of General Medical Sciences: $311,942.00
  • National Institute of General Medical Sciences: $299,322.00
  • National Institute of General Medical Sciences: $275,109.00
  • National Institute of General Medical Sciences: $46,964.00
  • National Institute of General Medical Sciences: $21,433.00
  • National Institute of General Medical Sciences: $277,888.00
  • National Institute of General Medical Sciences: $272,358.00
  • National Institute of General Medical Sciences: $300,999.00
  • National Institute of General Medical Sciences: $34,206.00
  • National Institute of General Medical Sciences: $240,441.00
  • National Institute of General Medical Sciences: $299,322.00
  • National Institute of General Medical Sciences: $299,322.00

ASJC

  • Molecular Biology
  • Oncology
  • Cancer Research
  • Cell Biology

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