Excessive production of inflammatory cytokines is prevented by the delivery of a molecular “one-two knockout punch” according to a report in Nature Immunology. These findings suggest a therapeutic target that might provide a means to limit tumor progression.
Chronic inflammation is associated with many types of metastatic cancer. Production of inflammatory cytokines is triggered by multiple signaling pathways that converge on the kinase Tak1 and lead to activation of the transcription factor NF-kappaB.
K Venuprasad and colleagues identify two enzymes, Cyld and Itch, that act together to modify Tak1, targeting it for destruction and thereby terminating the NF-kB activation process. Mice deficient for either Cyld or Itch express excessive amounts of tumor-promoting cytokines and develop larger and more metastatic tumors in experimental models of cancer.