Issues

Murray and colleagues as well as Hollstein and colleagues showed that the tumorigenic effects of disruption of the kinase LKB1, frequently mutated in lung cancer, are mediated by its downstream kinases SIK1 and SIK3. SIK1 and SIK3 acted synergistically, with their combined disruption leading to a tumor burden and average tumor size comparable to those of LKB1-deficient tumors in mouse lung cancer models. Histologic and molecular analyses revealed further overlap between the combined SIK1 and SIK3 mutants and LKB1 mutants. This pair of studies provides clarification of the mechanisms underlying the effects of LKB1 loss and provides a basis for further investigation and therapeutic targeting of the LKB1–SIK signaling axis in lung cancer. For details, please see the article by Murray and colleagues on page 1590 and the article by Hollstein and colleagues on page 1606.