A protein that plays an important role in turning normal tissue into cancer has been identified, which could be targeted with drugs in novel treatments for highly aggressive cancers affecting the brain, blood, skin, and kidney.
The RNA-modifying protein is known as METTL1 and its role in cancer was identified by researchers from the Wellcome Sanger Institute, University of Cambridge, and Harvard University. The researchers had used CRISPR-Cas9 in a previous study to identify potential vulnerabilities that could be targeted with new drugs for treating highly aggressive cancers. That study identified the METTL1 protein as one potential target.
Following on from that study, the researchers identified mutations in the METTL1 gene which resulted in higher than normal levels of the METTL1 protein being synthesized, which caused cells to replicate at a much faster rate and transform into a cancerous state. Overexpression of the METTL1 gene was implicated in the most aggressive tumors which have poor outcomes.
The researchers knocked out the METTL1 gene and cancer growth stopped, with no apparent effects on healthy cells in either their in vitro or in vivo studies on mice, which makes it a potentially good target for drug development.
Since levels of the METTL1 protein are elevated in some cancer cells, the protein could potentially serve as a biomarker that can be used to determine if patients would benefit from treatment with a new drug targeting the protein. Levels of the protein could also be used to determine which patients should take part in clinical trials to ensure they are as personalized as possible.
“Targeting RNA-modifying proteins can effectively destroy cancer cells and we hope that this research will provide the evidence necessary for drugs to be developed that target METTL1, potentially providing a new therapy against aggressive cancers with clear and unmet therapeutic need,” said Dr Konstantinos Tzelepis, who led the study.
You can read more about the study in the paper – METTL1-mediated m7G modification of Arg-TCT tRNA drives oncogenic transformation – which was recently published in the Molecular Cell. DOI: 10.1016/j.molcel.2021.06.031