肝脏是胃癌（GC）远端转移的主要靶点。肝转移前生态位（PMN）促进原发肿瘤和肝脏之间的重要通讯，从而在肝转移中发挥重要作用。鉴定GC中PMN形成的分子机制有助于制定预防和治疗肝转移的策略。在这里，我们发现了肝配蛋白 A1 (EFNA1) 信号在 PMN 发育中的作用。 GC 细胞中 EFNA1 的过表达通过 Hippo-YAP 途径显着增加了 CCL2 的分泌。分泌的 CCL2 通过 WNT/β-连环蛋白途径激活肝 PMN 内的肝星状细胞 (HStC)。抑制 CCL2 显着抑制 HStC 激活，并减少 GC 细胞中 EFNA1 信号传导引发的肝转移。此外，CCL2 高表达与 GC 患者的生存率较差相关。总体而言，这些研究结果表明，GC 细胞中的 EFNA1 信号传导上调 CCL2，从而激活 HStC，从而建立支持肝转移的肝转移前生态位。

The liver is a primary target for distal metastasis of gastric cancer (GC). The hepatic pre-metastatic niche (PMN) facilitates crucial communications between primary tumor and liver, thereby playing an essential role in hepatic metastasis. Identification of the molecular mechanisms driving PMN formation in GC could facilitate development of strategies to prevent and treat liver metastasis. Here, we uncovered a role for ephrin A1 (EFNA1) signaling in development of the PMN. EFNA1 overexpression in GC cells significantly increased CCL2 secretion through the Hippo-YAP pathway. Secreted CCL2 activated hepatic stellate cells (HStCs) within the hepatic PMN via the WNT/β-catenin pathway. Inhibition of CCL2 significantly suppressed HStC activation and reduced liver metastasis triggered by EFNA1 signaling in GC cells. Moreover, high CCL2 expression correlated with poor survival in GC patients. Overall, these findings reveal that EFNA1 signaling in GC cells upregulates CCL2, which activates HStCs to engender establishment of a hepatic pre-metastatic niche that supports liver metastasis.