Navigation Links
Cell death mystery yields new suspect for cancer drug development

A mysterious form of cell death, coded in proteins and enzymes, led to a discovery by UNC researchers uncovering a prime suspect for new cancer drug development.

CIB1 is a protein discovered in the lab of Leslie Parise, PhD , professor and chair of the department of biochemistry at the University of North Carolina at Chapel Hill. The small calcium binding protein is found in all kinds of cells.

Cassandra Moran, DO, was a pediatric oncology fellow at UNC prior to accepting a faculty position at Duke University. She is interested in neuroblastoma, a deadly form of childhood brain cancer. While working in the Parise lab at UNC as a resident, she found that decreasing CIB1 in neuroblastoma cells caused cell death.

Cancer is a disease of uncontrolled cell growth, so the ability to cause cancer cell death in the lab is exciting to researchers but the UNC team couldn't figure out how it was happening.

Tina Leisner, PhD, a UNC research associate in biochemistry, picked up where Dr. Moran left off when she returned to her clinical training.

"It was a mystery how loss of CIB1 was causing cell death. We knew that it wasn't the most common mechanism for programmed cell death, called apoptosis, which occurs when enzymes called caspases become activated, leading to the destruction of cellular DNA. These cells were not activating caspases, yet they were dying. It was fascinating, but frustrating at the same time," said Leisner.

What Dr. Leisner and her colleagues found, in the end, is that CIB1 is a master regulator of two pathways that cancer cells use to avoid normal mechanisms for programmed cell death. These two pathways, researchers believe, create "alternate routes" for cell survival and proliferation that may help cancer cells outsmart drug therapy. When one pathway is blocked, the other still sends signals downstream to cause cancer cell survival.

"What we eventually discovered is that CIB1 sits on top of two cell survival pathways, called PI3K/AKT and MEK/ERK. When we knock out CIB1, both pathways grind to a halt. Cells lose AKT signaling, causing another enzyme called GAPDH to accumulate in the cell's nucleus.Cells also lose ERK signaling, which together with GAPDH accumulation in the nucleus cause neuroblastoma cell death. In the language of people who aren't biochemists, knocking out CIB1 cuts off the escape routes for the cell signals that cause uncontrolled growth, making CIB1 a very promising drug target," said Dr. Parise.

This multi-pathway action is key to developing more effective drugs. Despite the approval of several targeted therapies in recent years, many cancers eventually become resistant to therapy.

"What is even more exciting," Leisner adds, "is that it works in completely different types of cancer cells. We successfully replicated the neuroblastoma findings in triple-negative breast cancer cells, meaning that new drugs targeted to CIB1 might work very broadly."

Contact: Ellen de Graffenreid
University of North Carolina Health Care

Related medicine news :

1. Higher-spending hospitals have fewer deaths for emergency patients
2. Reported Decline in U.S. Pneumonia Deaths May Be False: Study
3. Cancer Diagnosis May Raise Odds for Suicide, Heart Attack Death
4. Death From Accidental Injuries Among Kids Drops 30%: CDC
5. Opioids associated with highest risk of death
6. Study reveals major funding shortfall and high death rates for emergency laparotomy
7. Exercise helps smokers to quit smoking, to remain smoke-free and to reduce the risk of death
8. Additional blood pressure screening may reduce incidence of CVD events and death by up to 3 percent
9. Groundbreaking Nigeria summit results in major commitment to reduce child deaths
10. Measles Deaths Falling Worldwide
11. On-the-job deaths steady in Michigan; Number of burn injuries underreported
Post Your Comments:
(Date:11/28/2015)... ... 2015 , ... Trying to relax on a couch can actually be uncomfortable, ... this design due to personal experience with a bad back," he said. , This ... as well as increases support. It also makes it easier to eat, do other ...
(Date:11/27/2015)... ... ... There is only one major question facing all law firms in the 21st ... not been an easy question to answer. Especially when the senior partners and lawyers ... share the same discipline around working long hours. , In addition to this ...
(Date:11/27/2015)... ... November 27, 2015 , ... According to an article ... way that they are handling security in light of the recent terrorist attacks in ... an attempt to stop an attack from reaching U.S. soil. Especially around special events ...
(Date:11/27/2015)... ... November 27, 2015 , ... ... convenient way to dispense prescription medications at home, so he invented the patent-pending ... monitor and dispense prescription medications. In doing so, it could help to prevent ...
(Date:11/27/2015)... , ... November 27, 2015 , ... ... November 27th edition of USA Today in Atlanta, Dallas, New York, Minneapolis, South ... 750,000. The digital component is distributed nationally, through a vast social media strategy ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... November 26, 2015 ... "Self Administration of High Viscosity Drugs" report ... has announced the addition of the "Self ... their offering. --> Research and Markets ... the "Self Administration of High Viscosity Drugs" ...
(Date:11/25/2015)... -- The total global healthcare industry is expected to grow at ... America has the highest projected growth at 12.7%, ... ), is second with growth projected at 11.5%. ... expenditure. In 2013-2014, total government funded healthcare was nearly 68%. ... 41.2% in 2013-2014. In real terms, out of pocket expenditure ...
(Date:11/25/2015)... On Tuesday, November 24, 2015, the ... Wright Medical Technology, Inc. for product liability and ... implant device, awarded $11 million in favor of ... and three days of deliberations, the jury found ... designed and unreasonably dangerous, and that Wright Medical ...
Breaking Medicine Technology: