Metastasis is when cancer becomes deadly. Unsuccessful searches for driver mutations of metastasis have led some to explore alternative epigenetic causes. Pierce et al. found that the protein kinase LKB1, better known for influencing cancer through regulation of metabolism, had a tumor-suppressive role in one mouse lung cancer model. This tumor develops largely because of epigenomic effects on chromatin accessibility. Loss of LKB1 activates distinct waves of epigenetic remodeling in primary and metastatic tumor cells. Metastasis was mediated by activation of the transcription factor SOX17. The authors were then able to detect a small population of cells in primary tumors with the epigenetic characteristics of later metastatic cells, revealing a promising therapeutic target.
Nat. Cell Biol. 23, 915 (2021).