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Cancer

LKB1 cooperates with Sox17 to drive metastasis

Nature Cell Biology volume 23, pages 816–817 (2021)Cite this article

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LKB1 is frequently mutated in lung, cervical and other types of cancers. To determine how LKB1 inactivation contributes to lung cancer progression, Pierce et al. employed a chromatin accessibility assay to reveal Sox17 as a key transcription factor downstream of LKB1, promoting lung cancer metastasis.

Investigation of mechanisms delineating liver kinase B1 (LKB1 or STK11) contribution to cancer is complicated by the fact that it phosphorylates over a dozen kinases, which on their own have variety of targets involved in cell metabolism, growth and polarity1. One of the best characterised LKB1-regulated proteins belongs to the family of AMP-activated protein kinase (AMPK), which mediates cellular responses to nutrient availability. As a result, LKB1-mutated cells have a compromised AMPK pathway, making them vulnerable to metabolic drugs affecting AMP levels including metformin and phenformin2,3. Clinical trials are underway to determine the efficacy of this intervention combined with a fasting-mimicking diet for treating LKB1-deficient lung cancers.

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Fig. 1: LKB1 contribution to lung cancer progression and metastasis.

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  1. Ludwig Institute for Cancer Research, University of Oxford, Oxford, UK

    Skirmantas Kriaucionis

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  1. Skirmantas Kriaucionis
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Correspondence to Skirmantas Kriaucionis.

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Kriaucionis, S. LKB1 cooperates with Sox17 to drive metastasis. Nat Cell Biol 23, 816–817 (2021). https://doi.org/10.1038/s41556-021-00730-w

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