Epigenetic changes promoting cancer metastasis identified

December 21, 2016, University of Otago

Latest University of Otago research is shedding new light on why and how cancer cells spread from primary tumours to other parts of the body. This phenomenon – known as metastasis – causes about 90 per cent of all cancer deaths.

The Otago findings, published in the leading international journal Oncotarget, may pave the way for new therapies that prevent melanoma and other cancers from their deadly seeding of .

Department of Pathology researchers Dr Aniruddha Chatterjee and Professor Mike Eccles are lead authors of the study, which investigated in melanoma cells.

Epigenetics involves changes to the way genes behave – such as their being switched on or off through the addition of methyl groups to a gene's DNA segments.

After comparing primary and metastatic melanoma cells from the same patients, Dr Chatterjee says the research team identified thousands of epigenetic changes – and, crucially, several that were common to all the .

"We believe that these may be the key drivers that allow melanoma to metastasise," he says.

Additionally, the team identified a new function in melanoma of a gene called Early B Cell Factor 3 (EBF3).

"We found this gene gains more DNA methylation when primary melanoma progresses to its metastatic version, and that the gene expresses itself highly in the latter."

When the researchers used molecular techniques that decreased EBF3 expression, both primary and metastatic grew less aggressively and behaved less invasively.

Dr Chatterjee says earlier searches for genetic – rather than epigenetic – drivers of had not been very fruitful.

"Over the years, very few genetic mutations have been identified as drivers of metastasis. Instead, our approach looked at the changes in the way genes in are expressed, rather than changes to the genetic code itself," he says.

Dr Chatterjee says unlike genetic changes, epigenetic changes are reversible.

"So if we understand the key changes that underpin metastasis, then not only are we potentially able to monitor for their presence, but also to design new therapies to target and correct them to prevent metastasis of tumours."

Explore further: New research opens the 'black box' of malignant melanoma

More information: Chatterjee, A., Stockwell, P., Ahn, A., Rodger, E., Leichter, A., & Eccles, M. (2016). Genome-wide methylation sequencing of paired primary and metastatic cell lines identifies common DNA methylation changes and a role for EBF3 as a candidate epigenetic driver of melanoma metastasis. Oncotarget, 5. Retrieved from www.impactjournals.com/oncotar … 042&path%5B%5D=44772

Related Stories

New research opens the 'black box' of malignant melanoma

July 25, 2016
When malignant melanoma metastasizes to the brain, it is a death sentence for most patients. Metastatic melanoma is the deadliest of the skin cancers and the mechanisms that govern early metastatic growth and interactions ...

Epigenetic regulation of metastatic breast cancer progression may guide prognosis and future therapy

January 7, 2016
Boston-A gene that plays a role in the development of breast cancer to metastatic disease has been identified which may help to predict disease progression and serve as a target for the development of future breast cancer ...

Scientists discover a specific molecular biomarker for malignant melanoma

September 7, 2016
Melanoma is one of the types of cancer that poses the greatest challenge to researchers because it manifests in many ways, it contains a large number of mutations and displays high metastatic capacity. To date, clinicians ...

Researchers identify key role of microRNAs in melanoma metastasis

July 11, 2011
Researchers at the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center, identified for the first time the key role specific microRNAs (miRNAs) play in melanoma metastasis to simultaneously ...

Fighting melanoma's attraction to the brain

September 19, 2012
(Medical Xpress)—The process of metastasis, by which cancer cells travel from a tumor site and proliferate at other sites in the body, is a serious threat to cancer patients. According to the National Cancer Institute, ...

Discovery may lead to targeted melanoma therapies

June 17, 2015
Melanoma patients with high levels of a protein that controls the expression of pro-growth genes are less likely to survive, according to a study led by researchers at Icahn School of Medicine at Mount Sinai and published ...

Recommended for you

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

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.

Presurgical targeted therapy delays relapse of high-risk stage 3 melanoma

January 17, 2018
A pair of targeted therapies given before and after surgery for melanoma produced at least a six-fold increase in time to progression compared to standard-of-care surgery for patients with stage 3 disease, researchers at ...

Dulling cancer therapy's double-edged sword

January 17, 2018
Researchers have discovered that killing cancer cells can actually have the unintended effect of fueling the proliferation of residual, living cancer cells, ultimately leading to aggressive tumor progression.

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.