| First Author | Momcilovic M | Year | 2018 |
| Journal | Cancer Cell | Volume | 33 |
| Issue | 5 | Pages | 905-921.e5 |
| PubMed ID | 29763624 | Mgi Jnum | J:261866 |
| Mgi Id | MGI:6156738 | Doi | 10.1016/j.ccell.2018.04.002 |
| Citation | Momcilovic M, et al. (2018) The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma. Cancer Cell 33(5):905-921.e5 |
| abstractText | 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 GSK3alpha/beta signaling pathway, which upregulates glutaminolysis. Phospho-GSK3alpha/beta 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. |
