Research ArticleCell Biology

IKK promotes cytokine-induced and cancer-associated AMPK activity and attenuates phenformin-induced cell death in LKB1-deficient cells

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Science Signaling  10 Jul 2018:
Vol. 11, Issue 538, eaan5850
DOI: 10.1126/scisignal.aan5850

An inflammatory way to activate AMPK

In its best-known function as a sensor of energy status, the kinase AMPK is activated by phosphorylation mediated by the tumor suppressor LKB1. Antonia and Baldwin characterized a different pathway for AMPK activation involving TAK1, a kinase associated with inflammatory pathways. They found that this process required phosphorylation of AMPK by the TAK1 target IKK and that it occurred independently of LKB1 and, in certain cell lines, independently of TAK1 as well, indicating that TAK1-independent pathways that activate IKK could also stimulate AMPK. Combining an IKK inhibitor with the cancer drug phenformin improved its ability to kill LKB1-deficient cancer cells, highlighting a new potential treatment for cancers lacking this tumor suppressor.

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