A scientific team from the Center for Genomic Regulation (CRG) has identified several proteins involved in the progression of melanomathe deadliest form of cancer of skin.
As CRG reports in a press release, one of the proteins, PDIA6, is particularly importantand experiments in mice showed that melanoma cells with reduced levels of this protein had a reduced ability to metastasize to the lungs.
The scientific team discovered that PDIA6 promotes malignancy in melanoma binding to ribonucleic acid (RNA) molecules inside the tumor cell.
In the study, published in the journal Nucleic Acids Research and supported by the “la Caixa” Foundation, the region on the surface of PDIA6 that binds to RNA molecules is also identified.
This information can help design new therapeutic compounds that prevent the spread of melanoma from the skin to other parts of the body.
“PDIA6 has previously been linked to the progression of lymphoma, breast and lung cancer. If future studies confirm that PDIA6 also binds to RNA in these other cancers, the results could lead to a common therapeutic strategy in different tumours”emphasizes the CRG.
Fátima Gebauer, researcher at the CRG and lead author of the study, pointed out that “RNA-binding proteins are of great therapeutic interest; The technique used in this study makes it possible to measure its activity on a global scale, which is not possible with conventional methods.”
“When this technique is used to compare tumor and non-tumor cells, the method helps us identify which proteins might play an important role in cancer progression, and other experiments tell us how they work. We are using this strategy to discover new vulnerabilities in melanoma, and we hope it can be repeated to find new therapeutic targets in other cancer types as well,” he added.
More detailed analysis
Of the hundreds of RNA-binding proteins identified by the art, 24 were selected for further analysis using various criteriaincluding that their RNA-binding activity was not known or that they were not previously linked to cancer progression.
PDIA6 was chosen to further characterize its function, including transplantation experiments in mouse models. Future studies could be directed to analyze the relevance of the remaining 23 proteins.
“We only see the tip of the iceberg of the potential of RNA-binding proteins as therapeutic targets. Identification of RNA-binding activities by functional methods, followed by detailed molecular analysis of their capabilities, will aid in the design of inhibitors that can improve personalized cancer therapy,” Gebauer points out.
The work was carried out in collaboration with the University of Halle in Germany and the University of Oxford in the United Kingdom, with the support of the “la Caixa” Foundation through the CaixaResearch call for health research. The project started in 2014 funded by “La Marató” from TV3 and Catalunya Ràdio.