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Glutamine ratio is key ovarian cancer indicator
Date:5/5/2014

that targeting only glutaminase will miss the less aggressive ovarian cancer cells because they are at a metabolic stage where they are not yet glutamine-dependent."

Rice graduate student Lifeng Yang, lead author of the study, designed a preclinical experiment to test the feasibility of a multidrug approach. He used a drug to inhibit the early stage production of internal glutamine while also limiting the uptake of external glutamine.

"That depleted all sources of glutamine for the cells, and we found that cell proliferation decreased significantly," Yang said.

Nagrath said the study also revealed another key finding -- a direct relationship between glutamine and an ovarian cancer biomarker called STAT3.

"A systems-level understanding of the interactions between metabolism and signaling is vital to developing novel strategies to tackle cancer," said MD Anderson co-author Prahlad Ram, associate professor of systems biology and co-director of the MD Anderson Cancer Center's Systems Biology Program. "STAT3 is the primary marker that is used today to ascertain malignancy, tumor aggression and metastasis in ovarian cancer."

Nagrath said, "The higher STAT3 is, the more aggressive the cancer. For the first time, we were able to show how glutamine regulates STAT3 expression through a well-known metabolic pathway called the TCA cycle, which is also known as the Krebs cycle."

Nagrath said the research is ongoing. Ultimately, he hopes the investigations will lead to new treatment regimens for cancer as well as a better understanding of the role of cancer-cell metabolism in metastasis and drug resistance.


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Contact: Jade Boyd
jadeboyd@rice.edu
713-348-6778
Rice University
Source:Eurekalert  

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