Altered ribosomes help explain how an enzyme fuels tumor growth
A new Northwestern Medicine study has identified a previously unknown mechanism by which an enzyme promotes cancer cell proliferation, establishing it as a promising therapeutic target for cancer, according to findings published in Nature Communications.
Researchers at Northwestern Medicine have uncovered a novel mechanism by which the enzyme N-acetyltransferase 10 (NAT10) fuels the growth of cancer cells, potentially paving the way for new therapeutic strategies. NAT10, a protein with oncogenic properties, has been linked to various types of cancer, including liver cancer and leukemia.
Traditionally, its role in cancer has been linked to its ability to chemically modify RNA, but the exact significance of this function has been debated. To clarify NAT10's role, scientists employed an advanced functional genomics technique, creating a library of 1,900 mutant versions of the protein with single amino acid substitutions each.
These mutants were then introduced into a proliferation assay, where they competed against one another in cell growth. The results showed that all mutants impairing cell proliferation were found in the RNA helicase domain of NAT10, not its RNA acetyltransferase activity. Validation through biochemical, cellular, and animal models confirmed that the RNA helicase domain, not the RNA acetyltransferase function, is crucial for cancer cell proliferation and tumor growth.
The researchers discovered that NAT10's RNA helicase activity leads to the production of cancer-specific ribosomes with a reduced chemical modification, m1acp3Y, which is commonly lower in tumor cells. By targeting this helicase domain, scientists may discover a novel therapeutic approach to halt cancer cell proliferation.
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