Melanoma cells rely on a gene involved in nerve development in order to spread, according to research conducted at the Institute for Cancer Research (ICR), London.
The gene, ARHGEF9, drives the creation of structures called filopodia, which are involved in the growth and development of new nerves. However, melanoma cells are able to use the gene to also create filopodia, which act as 'molecular drills' to penetrate and disturb the surrounding area, leading to metastasis – a process by which cancer can spread. This suggests that blocking the gene may stop cancer from spreading.
'Our work shows that melanoma cells borrow use of ARHGEF9 from nerve cells to change shape, branch out and invade new tissues' said Chris Bakal, professor of cancer morphodynamics at ICR, who led the study. 'It's incredibly important that we understand how cancer cells change their shape to become more aggressive and invasive. When cancers metastasise, they become much harder to treat.'
The research, which was published in iScience, involved depleting genes individually, then analysing how these changes altered the shapes of growing melanoma cells. These were grown in bioengineered 3D matrices, and the filopodia were visualised using sophisticated microscopy techniques.
It is also suggested that ARHGEF9 may drive development of other cancers, in particular neuroblastoma which arises from nerve cells. However, these results are especially significant for treating melanoma, the rates of which have doubled in the past thirty years.
'The majority of cancer deaths occur because cancer has spread from the original tumour to other parts of the body' said Professor Clare Isacke, the dean of academic and research affairs at ICR, who described the results as 'a fundamental discovery about how melanoma cells manipulate their shape to become invasive'.
Further research will aim to explore the extended effects of blocking ARHGEF9 to prevent metastasis, as well as shed light on the mechanisms by which cancer cells grow and interact.
Professor Isacke added, 'Although it is early research, and more work needs to be done, by understanding more about how skin cancer spreads, we could open up new avenues for developing treatments which stop cancer in its tracks'.
Sources and References
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Skin cancer cells harness nerve cell gene to drill through and invade new tissues
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ARHGEF9 regulates melanoma morphogenesis in environments with diverse geometry and elasticity by promoting filopodial-driven adhesion
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Research on ‘molecular drills’ of skin cancer cells offers hope for treatment
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Metastasizing melanoma cells hijack gene involved in development of the nervous system
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Scientists discover how melanoma invades new tissue
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