Newly found enzymes may play early role in cancer

December 24, 2008

Researchers have discovered two enzymes that, when combined, could be involved in the earliest stages of cancer. Manipulating these enzymes genetically might lead to targeted therapies aimed at slowing or preventing the onset of tumors.

"We could conceivably reactivate a completely normal gene in a tumor cell - a gene that could prevent the growth of a tumor if reactivated," says David Jones, Ph.D., professor of oncological sciences at the University of Utah and senior director of early translational research at the university's Huntsman Cancer Institute (HCI).

"We believe this could be one of the earliest processes to go wrong in cancer," he adds. "By manipulating these enzymes, we could possibly prevent or slow the onset of tumors."

The enzymes appear to control an "on-and-off switch" for critical genes that could trigger cancer or numerous other diseases and birth defects. The research is published in the December 26 issue of Cell.

Using zebrafish that share similar genetics to humans, the HCI scientists identified a previously unknown enzyme process that controls the levels of DNA methylation on genes.

"Methylation is a cellular process that is required for healthy cell growth and development, but it can go awry in cancer and diseased cells," says Brad Cairns, Ph.D., HCI investigator and professor of oncological sciences at the University of Utah. "You can think of DNA methylation as an on-and-off switch. Methylation silences or 'shuts off' genes that need to be turned off or are not functioning as they should, whereas the reverse process called demethylation 'turns on' healthy genes and genes needed at critical times in development," he says.

In cancer, this methylation process goes haywire, leading to tumor growth. Genes that should be "turned on" are not and vice versa.

The significance of this research is the discovery of two enzymes involved in DNA demethylation. Defects in DNA methylation balance are strongly associated with the early development of cancer, other diseases and birth defects, and the scientists say their study is the first clear evidence that this enzyme system plays a critical role in maintaining this balance. They also believe it's a process that can be reversed.

Further research will reveal if DNA methylation levels can be manipulated genetically. If so, it could lead to drugs to reactivate particular genes and suppress tumor growth. Remarkably, this system also helps protect the genome from mutations.

"We discovered a pair of enzymes that can remove methylated DNA, but if these enzymes work improperly, they will instead enhance the rate of mutations in methylated DNA and cause cancer progression," says Jones. "The question now is, when they work improperly, can we find ways to shut them off and prevent these mutations?"

The enzymes leading to DNA demethylation involve the coupling of a 5-meC deaminase enzyme, a G:T glycosylase enzyme and Gadd45, which is not an enzyme.

Source: University of Utah

Explore further: Researchers identify epigenetic orchestrator of pancreatic cancer cells

Related Stories

Researchers identify epigenetic orchestrator of pancreatic cancer cells

December 11, 2017
Genentech researchers have identified an enzyme that shifts pancreatic cancer cells to a more aggressive, drug-resistant state by epigenetically modifying the cells' chromatin. The study, which will be published December ...

Insights on how SHARPIN promotes cancer progression

December 11, 2017
Researchers at Sanford Burnham Prebys Medical Discovery (SBP) and the Technion in Israel have found a new role for the SHARPIN protein. In addition to being one of three proteins in the linear ubiquitin chain assembly complex ...

Researchers bring new insight into Chediak-Higashi syndrome, a devastating genetic disease

December 12, 2017
A team of researchers from the National Institutes of Health and University of Manchester have uncovered new insights into a rare genetic disease, with less than 500 cases of the disease on record, which devastates the lives ...

In multiple myeloma, high levels of enzyme ADAR1 are associated with reduced survival

December 5, 2017
Multiple myeloma is the second most common blood cancer in the United States. Thirty to 50 percent of multiple myeloma patients have extra copies of the gene that encodes the enzyme ADAR1. Using a database of multiple myeloma ...

Scientists take early step to personalized breast cancer care

November 29, 2017
UT Southwestern Medical Center researchers have developed a method to map protein changes that occur in different subtypes of breast cancer cells in response to DNA damage from a new class of chemotherapy drugs.

Researchers discover BRCA cancer cells' last defense

November 28, 2017
In a new paper published in Nature Communications, a team led by Saint Louis University researcher Alessandro Vindigni, Ph.D. shares new information about how BRCA-deficient cancer cells operate, interact with chemotherapy ...

Recommended for you

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

Liquid biopsy results differed substantially between two providers

December 14, 2017
Two Johns Hopkins prostate cancer researchers found significant disparities when they submitted identical patient samples to two different commercial liquid biopsy providers. Liquid biopsy is a new and noninvasive alternative ...

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.