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.

中文翻译：

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黑色素瘤利用局部线索促进肝脏特异性转移

使用 CRISPR-Cas9 筛选，我们发现癌细胞固有的 Pip4k2c 缺失通过选择不同的肝脏代谢线索对胰岛素介导的 PI3K-AKT 信号超敏而赋予黑色素瘤肝转移性器官向性。此外，我们还发现，消除生理和药物引起的葡萄糖和胰岛素水平变化的组合疗法可以特异性减少肝转移。