Cell death mystery yields new suspect for cancer drug development

September 13, 2012, University of North Carolina Health Care

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 . While working in the Parise lab at UNC as a resident, she found that decreasing CIB1 in caused cell death.

Cancer is a disease of , 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 . 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 use to avoid normal mechanisms for . These two pathways, researchers believe, create "alternate routes" for 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."

Explore further: Research identifies how cancer cells cheat death

More information: The team's findings were published in the journal Oncogene.

Related Stories

Research identifies how cancer cells cheat death

June 8, 2011
Research led by David Litchfield of The University of Western Ontario has identified how biochemical pathways can be "rewired" in cancer cells to allow these cells to ignore signals that should normally trigger their death. ...

Plant flavonoid luteolin blocks cell signaling pathways in colon cancer cells

January 23, 2012
Plant flavonoid luteolin blocks cell signaling pathways in colon cancer cells

Recommended for you

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Dietary fat, changes in fat metabolism may promote prostate cancer metastasis

January 15, 2018
Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.