Two enzymes work together to promote tumor growth: Study

DALLAS, Dec. 14 (UPI) — Researchers at The University of Texas at Dallas have discovered a link between two enzymes that in tandem may actually work to promote tumor growth in cancer patients.

Dr. Jung-Whan Kim, assistant professor of biological sciences and co-lead author of the study, examined the enzymes NQO1 and HIF-1a. On its own, NQO1 helps protect the body from cancer-causing damage of free radicals and environmental toxins like cigarette smoke.

HIF-1a aids in cell survival when oxygen levels in the body are temporarily low, a condition known as hypoxia. When optimal oxygen levels return, HIF-1a is degraded.

“There has been no reason to suspect these two proteins interact, but now we know they do,” Kim said in a press release. “This finding was totally unexpected.”

The findings, which were published in Nature Communications, reveal that NQO1 binds to HIF-1a and that by binding to HIF-1a in cancer cells, NQO1 regulates the partner protein by stabilizing it, preventing HIF-1a from being downgraded.

“Cancer cells, like any other cells, need oxygen to survive, but they grow really fast so they become hypoxic – therefore, they suffer from low oxygen,” Kim said in a press release. “They try to adapt to or overcome this hypoxic stress through various mechanisms, one of which is to increase HIF-1a. This enzyme signals the body to make more blood vessels to feed the tumor and to reprogram cellular metabolism to adapt to hypoxia. Until now, though, no one had made a connection between HIF-1a and NQO1.”

For the study, researchers examined colorectal cancer cells obtained from patients and found a significant link between high NQO1 and high HIF-1a levels. In other experiments, researchers eliminated the NQO1 in colorectal and breast cancer cells then injected these modified cells into immunocompromised mice while a control group received unmodified tumor cells.

“We saw tumor levels drop in mice that received cancer cells without NQO1,” Kim stated in a press release. “Our experiments strongly suggest that this tumor growth was inhibited specifically through reduced NQO1-dependent HIF-1a activity.”

The team is currently examining the role HIF-1a plays in certain types of lung cancer. He is working the Dr. Jung-Mo Anh, associate professor of chemistry and biochemistry, to identify molecules that may target and block HIF-1a in cancer cells.