API2-MALT1 fusion protein appears to trigger cancer

What happens when two proteins join together? In this case, they become like a power couple, where the whole is greater than the sum of the parts. API2 and MALT1 are two proteins that become fused together in a subset of lymphomas. The API2 part of the fusion connects with an enzyme called NIK. When it does, MALT1 comes in for the kill, splitting NIK in two, a process called cleavage.

"A particularly exciting feature to this discovery is that the critical cancer-causing event involves a kinase — NIK — and a protease — API2-MALT1. Both kinases and proteases are considered druggable, meaning they are potential targets for developing drugs that block their activity," says Lucas, assistant professor of pathology at the U-M Medical School.

MALT lymphomas that carry the API2-MALT1 fusion protein tend to be more aggressive and more resistant to treatment. The result is larger tumors and increased spread throughout the body.

The researchers found that once NIK becomes stable, it triggers a series of downstream reactions that make cells more likely to metastasize and more resistant to current treatments.

These effects were reversed when researchers turned off NIK, suggesting that either blocking NIK or preventing NIK from becoming stable by blocking the protein fusion, could halt the growth and spread of MALT lymphoma tumors.

While NIK inhibitors are being investigated, these therapies are not currently available.

Source: University of Michigan

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