A new unexpected key player in melanoma development identified

May 3, 2017
Melanoma in skin biopsy with H&E stain — this case may represent superficial spreading melanoma. Credit: Wikipedia/CC BY-SA 3.0

Identification and functional validation of proteins involved in tumorigenesis are essential steps toward advancing cancer precision medicine. In the Journal of Clinical Investigation researchers from VIB, KU Leuven (Belgium) together with colleagues from INSERM (France) now report the important role for FES in the initiation and progression of melanoma, a malignant type of skin cancer, that is notoriously quick to metastasize and that responds poorly to existing cancer treatments. Unexpectdly the expression of FES, which encodes a kind of protein better known for their ability to promote cancer development-, is lost in a large fraction of human melanoma. The researchers also identified a pharmacological way through which FES expression can be restored in human melanoma. This can be the first step in a novel therapeutic strategy against melanoma.

Human melanoma is a very aggressive skin cancer, but very little is known about the mechanisms that cause the disease to progress. The fact that melanoma often exhibits UV-induced genetic alterations makes it, among other features, a very complex disease to study. Prof. Jean-Christophe Marine (VIB-KU Leuven) and others developed mouse models recapitulating some of the key histopathological features of the human disease. Importantly, the mouse melanoma lesions are far less complex than their human counterparts. Taking advantage of these 'simplified' versions of melanoma, the researchers identified a dozen of new genes that are likely to play key roles in the initiation and/or progression of human melanoma. To further validate their findings, they studied the role of one of the genes, namely FES, and established its important contribution to the development of both mouse and human melanoma.

An oncogene that suppresses melanoma tumor growth via a key cancer pathway

Previous research identified FES as an 'oncogene' – a gene that is able to transform a normal cell into a cancer cell under certain conditions – in leukemia, for example. However, its role in melanoma appears very different.

Prof. Jean-Christophe Marine (VIB-KU Leuven): "To our surprise we obtained clear evidence that FES strongly suppresses melanoma growth and viability. Its expression is silenced in more than 30% of human melanoma lesions. Importantly, we showed that FES deletion in mice accelerated the growth of melanoma tumors."

The research team also showed that FES modulates the WNT signaling pathway. This key pathway is activated in virtually all melanoma, but the mechanisms that contribute to this activation remain largely unclear. So this study provides one route through which this pathway is activated in about 30% of the cases.

Pharmacological implications of FES

Prof. Marine and his research team also identified a pharmacological way of restoring the expression of FES in human melanoma. The approach involved the use of epigenetic drugs that promote DNA demethylation; some of which are currently tested in clinical trials for . It will be interesting to assess whether the efficacy of these drugs can be linked, at least partly, to restoration of FES expression.

Prof. Jean-Christophe Marine: "We will definitely further explore this new putative therapeutic strategy. Importantly, in the same time our data raise concerns about ongoing clinical trials with broad spectrum tyrosine kinase inhibitors. Some of these inhibitors inactivate FES and therefore may lead to undesired effects."

Explore further: Team achieves breakthrough in diagnosis of melanoma skin cancer

More information: Comparative oncogenomics identifies FES as a tumor suppressor in melanoma, Olvedy et al. Journal of Clinical Investigation, May 2017

Related Stories

Team achieves breakthrough in diagnosis of melanoma skin cancer

March 23, 2016
In collaboration with researchers from UGent, VIB scientists from KU Leuven have revealed a remarkable link between malignant melanoma and a non-coding RNA gene called SAMMSON. The SAMMSON gene is specifically expressed in ...

Scientists identify gene that regulates the growth of melanoma

February 29, 2016
Yale Cancer Center researchers have identified a gene in melanoma that can dramatically affect the growth of the disease. The findings, published in the journal Cell Reports, provide new insight into how melanoma grows and ...

Researchers identify key mutation that suppresses the immune system in melanoma

March 7, 2017
University of California, Irvine researchers have identified a specific mutation that allows melanoma tumor cells to remain undetected by the immune system. The finding may lead to the development of better immunotherapies ...

Epigenomic changes play an important role during the progression of melanoma

April 9, 2015
KU Leuven researchers have zeroed in on what makes cancer cells in melanoma so aggressive. They also succeeded in taming the effect in cell cultures. Melanoma, a type of skin cancer, is notoriously quick to metastasize and ...

A tiny RNA with a big role in melanoma

February 18, 2014
A Yale-led study has identified a key mechanism in the regulation of gene expression that promotes the proliferation of melanoma cells. The finding opens a possible avenue for development of treatments that target this mechanism. ...

A protein that defines the melanoma blueprint

November 18, 2016
The main goals of the Melanoma Group at the Spanish National Cancer Research Centre (CNIO) are to identify biomarkers of tumour progression and to validate novel therapeutic targets in melanoma. In particular, their research ...

Recommended for you

One in five young colon cancer patients have genetic link

December 13, 2017
As doctors grapple with increasing rates of colorectal cancers in young people, new research from the University of Michigan may offer some insight into how the disease developed and how to prevent further cancers. Researchers ...

New strategy for unleashing cancer-fighting power of p53 gene

December 13, 2017
Tumor protein p53 is one of the most critical determinants of the fate of cancer cells, as it can determine whether a cell lives or dies in response to stress. In a new study published today in the journal Nature Communications, ...

Researchers develop test that can diagnose two cancer types

December 12, 2017
A blood test using infrared spectroscopy can be used to diagnose two types of cancer, lymphoma and melanoma, according to a study led by Georgia State University.

Cancer-causing mutation suppresses immune system around tumours

December 12, 2017
Mutations in 'Ras' genes, which drive 25% of human cancers by causing tumour cells to grow, multiply and spread, can also protect cancer cells from the immune system, finds a new study from the Francis Crick Institute and ...

Atoh1, a potential Achilles' heel of Sonic Hedgehog medulloblastoma

December 12, 2017
Medulloblastoma is the most common type of solid brain tumor in children. Current treatments offer limited success and may leave patients with severe neurological side effects, including psychiatric disorders, growth retardation ...

MRI scans predict patients' ability to fight the spread of cancer

December 12, 2017
A simple, non-invasive procedure that can indicate how long patients with cancer that has spread to the brain might survive and whether they are likely to respond to immunotherapy has been developed by researchers in Liverpool.

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.