Study pinpoints epigenetic function of common cancer-causing protein—it's not what science thought

September 26, 2012 by Garth Sundem, University of Colorado Denver

(Medical Xpress)—Squamous cell carcinoma (SCC) is diagnosed in about 700,000 people in the United States every year. Commonly contributing to SCC is a protein called DNp63a – it goes abnormally high and the ability of a patient's body to kill cancer cells goes abnormally low. In many cases of SCC, it's just that simple. And science thought the function of DNp63a was simple, as well: the tumor suppressor gene p53 is responsible for recognizing and killing cancer cells, and in SCC, it's usually inactivated. It looked like high DNp63a repressed p53, made SCC.

A University of Colorado Cancer Center study published today in the journal & Development throws the accepted role of DNp63a on its ear. Though high DNp63a and low p53 activity are correlated in SCC, there's no causation – DNp63a doesn't affect p53. Instead, DNp63a employs "epigenetics" to keep alive.

"This is a potent oncogene whose mechanism we thought we knew. But basically in this paper we demolish the accepted model. DNp63a doesn't work through p53 – it operates through epigenetic silencing of anti-proliferative genes," says the study's senior author, Joaquin M. Espinosa, PhD, investigator at the CU Cancer Center and associate professor in the Department of Molecular, Cellular and Developmental Biology at CU Boulder.

Genes are blueprints that code for proteins and these proteins in turn drive most things that happen in the body, both good and bad. But between genes and their protein products is the layer of epigenetics – genes may be expressed differently depending on the heritable, epigenetic features that turn them on and off. In the case of DNp63a, it employs a protein partner called H2A.Z, which in volume effectively buries anti-proliferative genes in silt, rendering them unable to go about their anti-cancer duties.

"Independently of p53, DNp63a is shutting down genes that stop cell division – shutting down anti-proliferative genes so that cells can keep dividing and dividing and dividing," Espinosa says.

Now that the function of DNp63a is known, Espinosa is looking inside the chain of events for a breakable link.

"DNp63a itself isn't druggable," he says, "but the enzymes that partner with DNp63a for epigenetic silencing are."

With a mechanism in hand, Espinosa and colleagues can now explore in animal models the possible effects of breaking the DNp63a mechanism. Drug away an essential enzyme and DNp63a may lose its ability to cause cancer.

Explore further: Cell differentiation as a novel strategy for the treatment of an aggressive type of skin cancer

Related Stories

Cell differentiation as a novel strategy for the treatment of an aggressive type of skin cancer

July 9, 2012
Skin squamous cell carcinoma (SCC) is a subtype of very aggressive skin cancers that usually develops in sunexposed body regions, but can also affect a large number of organs such as the bladder, esophagus, lungs etc. However, ...

Drug kills cancer cells by restoring faulty tumor suppressor

May 14, 2012
A new study describes a compound that selectively kills cancer cells by restoring the structure and function of one of the most commonly mutated proteins in human cancer, the "tumor suppressor" p53. The research, published ...

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

Study advances gene therapy for glaucoma

January 16, 2018
While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains ...

How incurable mitochondrial diseases strike previously unaffected families

January 15, 2018
Researchers have shown for the first time how children can inherit a severe - potentially fatal - mitochondrial disease from a healthy mother. The study, led by researchers from the MRC Mitochondrial Biology Unit at the University ...

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.