The serine/threonine liver kinase B1 (LKB1) is a tumor suppressor and a well-established activator of AMPK kinases involved in cellular meta-bolism. In addition to restricting tumor growth, LKB1 has also been shown to limit the metastatic potential of tumor cells, but it is unclear if this is dependent on AMPK. Pierce and colleagues described a novel function of this kinase by showing that LKB1 regulates chromatin accessibility, mediated via the SIK family of kinases in lung cancer. High levels of the transcription factor SOX17 and increased accessibility of genomic regions that contain SOX motifs correlated with metastatic progression in LKB1-deficient mouse lung adenocarcinomas. Interestingly, some primary lung tumors contained a metastatic-like population of SOX17+ cells, with SOX17 being sufficient to drive epigenetic changes in LKB1-deficient cells that drive metastases.

Expert Commentary: The identification of epigenetic differences in primary tumors and metastatic lesions driven by LKB1 loss highlights the ability...

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