Grants and Contracts Details
Lung cancer, in particular, non-small cell lung cancer (NSCLC) is the most common and fatal cancer in Kentucky. Like all other cancer cells, NSCLC cells are heavily dependent on glucose consumption via lactic fermentation (the Warburg effect) to satisfy energy needs for growth and proliferation. The Warburg effect is a key metabolic hallmark of cancer cells, and its inhibition often leads to growth retardation and tumor regression. Sulfiredoxin (Srx) is a novel oxidoreductase that restores the peroxidase activity of peroxiredoxin (Prx) to maintain cellular redox balance, and is also a regulator of cellular redox-related signaling. We have demonstrated that Srx is highly expressed in tumor specimens of NSCLC patients but absent in cancer adjacent normal and pulmonary tissue of healthy individuals. Targeted depletion of Srx in NSCLC cells not only leads to the inhibition of colony formation and cell invasion in vitro, but also represses tumor xenograft growth and abolishes cells’ ability to form metastasis in mouse lung in vivo. However, mechanisms by which Srx promotes lung cancer development have not been fully understood. In particular, whether Srx plays a role in cancer cell metabolism has not been reported in the literature. Our preliminary data demonstrate that targeted depletion of Srx in NSCLC cells leads to the inhibition of glycolysis Therefore, we hypothesize that Srx functions as a metabolic switch in NSCLC cells to determine the route of glucose metabolism by regulating critical metabolic enzymes. Through collaboration with experts in metabolism, clinic, informatics, statistics and pathology, we expect to (1) demonstrate that the presence of Srx in NSCLC cells promotes glucose metabolism through glycolysis; (2) determine the molecular mechanism by which Srx directs glucose metabolism to glycolysis in NSCLC cells; (3) determine the value of using Srx alone, or a combination with PFK1 or 6PGL, as biomarker to predict the prognosis of NSCLC patients.
|Effective start/end date||1/1/18 → 12/31/23|
- KY Lung Cancer Research Fund: $150,000.00
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