Using CRISPR–Cas9 screens, we found that cancer-cell-intrinsic loss of Pip4k2c conferred liver-metastatic organotropism in melanoma through hypersensitization to insulin-mediated PI3K–AKT signaling via co-optation of distinct hepatic metabolic cues. Additionally, we showed that combinatorial therapies that abolished physiological and drug-induced changes in glucose and insulin levels specifically reduced liver metastasis.
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This is a summary of: Rogava, M. et al. Loss of Pip4k2c confers liver-metastatic organotropism through insulin-dependent PI3K-AKT pathway activation. Nature https://doi.org/10.1038/s43018-023-00704-x (2024).
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Melanoma leverages local cues to promote liver-specific metastasis. Nat Cancer 5, 380–381 (2024). https://doi.org/10.1038/s43018-023-00705-w
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DOI: https://doi.org/10.1038/s43018-023-00705-w
