A new study has identified a non-enzymatic role for METTL3 in breast cancer progression, showing the protein facilitates secretion of pro-invasive molecules from the cytoplasm – suggesting that current strategies targeting its enzymatic activity alone may be insufficient to halt tumour spread.
Researchers at Umeå University have identified a previously unknown role for the protein METTL3 that helps breast cancer cells spread, which could inform new future cancer therapies.
The study found that METTL3 enables tumours to invade surrounding tissue and form metastases by regulating the release of molecules from cancer cells.
Scientists say the findings reveal an entirely new function for the protein, which has already been linked to several forms of cancer.
“We discovered that METTL3 has a different function, which may be just as important for cancer progression as the one previously known,” says Margalida Esteva Socias, a research assistant at the Department of Molecular Biology at Umeå University and co-first author of the study.
New role identified
METTL3 is already well known for regulating chemical modifications of RNA within cells. By adding molecular marks to RNA, it helps control which genes are active. Abnormal activity of the protein has previously been associated with several cancers and drugs designed to target its function are already being tested in clinical trials.
However, the latest research shows that METTL3 also plays a separate role in helping breast cancer cells spread.
METTL3 is already well known for regulating chemical modifications of RNA within cells
The team discovered that the protein moves from its usual location in the cell nucleus into the cytoplasm, where it becomes part of a transport system used by cancer cells to release molecules into surrounding tissue.
Researchers found that METTL3 supports this transport system, increasing the secretion of proteins that enable cancer cells to invade healthy tissue and spread throughout the body.
Reduced spread after protein removal
When METTL3 was removed from breast cancer cells, the researchers observed that fewer of these proteins were released. The cells became less invasive and partially lost their ability to break down surrounding tissue, limiting their capacity to spread.
Importantly, the same effects could not be achieved simply by blocking the protein’s enzymatic activity. This suggests METTL3 promotes cancer progression through additional mechanisms beyond its established role in RNA modification.
When METTL3 was removed from breast cancer cells, the researchers observed that fewer of these proteins were released
The study also found that reducing METTL3 levels slowed tumour growth and delayed the formation of lung metastases in experimental models.
“Our results indicate that in some cancers, it may not be sufficient to block the enzymatic activity of METTL3. Fully inhibiting its tumour-promoting effects may require strategies that eliminate the entire protein or disrupt its interactions within the cell,” says Francesca Aguilo, Associate Professor at the Department of Molecular Biology at Umeå University and a principal investigator of the study.
Potential impact on future therapies
The findings give scientists a better understanding of how cancer cells alter their surrounding environment to support invasion and metastasis, offering researchers a potential new target for future therapies.
The next stage of the research will investigate how METTL3 relocates from the nucleus to the cytoplasm and whether the same mechanism is involved in other forms of cancer.
The findings provide fresh insight into how cancer cells alter their surrounding environment to support invasion and metastasis
If confirmed, the discovery could help inform the development of new treatments designed to prevent cancer spread by targeting the protein’s newly identified function, rather than focusing solely on its enzymatic activity.
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