Nav: Home

UT Dallas scientist discovers new cancer connection

December 14, 2016

A biologist at The University of Texas at Dallas and his colleagues have discovered that two enzymes previously linked independently with keeping cancer cells alive actually work in tandem to spur tumor growth.

"There has been no reason to suspect these two proteins interact, but now we know they do. This finding was totally unexpected," said Dr. Jung-Whan (Jay) Kim, assistant professor of biological sciences and co-lead author of the study published Dec. 14 in the online journal Nature Communications.

The two enzymes Kim studied are abbreviated NQO1 and HIF-1a (pronounced "hif-one-alpha"). Under normal biological conditions, NQO1 helps protect the body from the cancer-causing damage of free radicals and environmental toxins, such as cigarette smoke. HIF-1a aids cell survival when oxygen levels in the body are temporarily low, a condition known as hypoxia. As optimal oxygen levels return, HIF-1a is degraded.

In many types of cancer tumors, however, both enzymes occur persistently at very high levels. Elevated NQO1 expression, in particular, is associated with poor prognosis in breast, colon, cervical, lung and pancreatic cancer patients, although the molecular mechanism for the elevated expression remains unclear.

Kim's group discovered a likely explanation.

"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. "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," Kim said.

Kim's research group conducted a series of experiments to determine which of several proteins interact with HIF-1a. Unexpectedly, they found that NQO1 binds to HIF-1a to form a complex.

"We confirmed that they [HIF-1a and NQO1] are bound together and interacting. We also determined where in their structure they physically connect," said Kim, whose co-authors include biology graduate student Justin Goodwin BS'15, former research associate Robin Ruthenborg BS'13 MS'14 and several colleagues in South Korea. "We also characterized what happens biochemically when these two proteins are bound together."

The results show that by binding to HIF-1a in cancer cells, NQO1 regulates the partner protein by stabilizing it, preventing HIF-1a from being degraded.

"We have revealed this novel function for NQO1 in stabilizing HIF-1a, which, in turn, enhances tumor growth," Kim said.

As part of their study, the researchers examined colorectal cancer cells obtained from patients and found a significant correlation between high NQO1 and high HIF-1a levels. "Our observations provided strong supportive evidence that the two proteins physically interact," Kim said.

In subsequent experiments, the group eliminated NQO1 in colorectal and breast cancer cells. They injected the modified cells into immunocompromised mice, whose inhibited immune systems are capable of growing human tumors. A group of control animals received unmodified tumor cells.

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

Kim's UT Dallas research team is currently investigating the role of HIF-1a in certain types of lung cancers and is collaborating with Dr. Jung-Mo Anh, associate professor of chemistry and biochemistry, to identify molecules that might target and block HIF-1a in cancer cells.

"We have some potentially interesting candidates, but we need further research," Kim said. "We are in the very early stages, but hopefully we will see some inhibitors emerge within the next few years."
The research reported in Nature Communications was supported by the National Research Foundation of Korea.

University of Texas at Dallas

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.