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Publication

The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma.

Cancer cell | 2018

Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/β signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/β protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance. In addition, we identified a conserved metabolic signature in a broad spectrum of hypermetabolic human tumors that may be predictive of patient outcome and response to combined metabolic therapies targeting mTOR and glutaminase.

Pubmed ID: 29763624 RIS Download

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Associated grants

Agency: NCATS NIH HHS, United States
Id: KL2 TR000122
Agency: NCATS NIH HHS, United States
Id: UL1 TR000124
Agency: NCI NIH HHS, United States
Id: P30 CA016042
Agency: NHLBI NIH HHS, United States
Id: T32 HL072752
Agency: NCI NIH HHS, United States
Id: P01 CA168585

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GraphPad Prism (tool)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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amide (tool)

RRID:SCR_005940

Software tool for viewing, analyzing, and registering volumetric medical imaging data sets. It has been written on top of GTK+ and runs on any system that supports this toolkit (Linux, Windows, Mac OS X, etc.). The program incorporates automatic non-orthogonal data reslicing, allowing multiple data set to be fused without imposed constraints on the dimensions, anisotrophy, or voxel sizes of the data. Additional features include 3D ROI (ellipses, cylinders, boxes, and isocontours), multi-slice viewing, volume rendering, and data importing through the (X)MedCon library.

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