Mucosa-associated lymphoid tissue (MALT) lymphoma, a type of B cell lymphoma, is associated with chronic inflammation. Many patients are successfully treated with antibiotics; however, patients whose lymphomas express the API2-MALT1 fusion oncoprotein as a result of a chromosomal translocation are resistant to this therapy. API2-MALT1–driven lymphomagenesis is associated with deregulated canonical nuclear factor κB (NF-κB) signaling; however, Rosebeck et al. now demonstrate that noncanonical NF-κB signaling may also play a role. API2-MALT1, but not wild-type MALT1, cleaved the noncanonical NF-κB signaling intermediate, NF-κB–inducing kinase (NIK), driving constitutive noncanonical NF-κB signaling. API2-MALT1–expressing cells exhibited great resistance to apoptosis and enhanced integrin-mediated adhesion, both of which were NIK-dependent. Tumor samples from patients with API2-MALT1–expressing tumors expressed higher levels of noncanonical NF-κB genes compared with API2-MALT1–negative tumors. Thus, both canonical and noncanonical NF-κB signaling are likely to contribute to MALT lymphomagenesis.
S. Rosebeck, L. Madden, X. Jin, S. Gu, I. J. Apel, A. Appert, R. A. Hamoudi, H. Noels, X. Sagaert, P. Van Loo, M. Baens, M.-Q. Du, P. C. Lucas, L. M. McAllister-Lucas, Cleavage of NIK by the API2-MALT1 fusion oncoprotein leads to noncanonical NF-κB activation. Science 331, 468–472 (2011). [Abstract] [Full Text]