胃癌患者（GC）的死亡主要是由癌细胞的转移所致。大量证据表明，肿瘤相关巨噬细胞在促进肿瘤浸润和转移方面起着重要作用；然而，在GC中肿瘤细胞与巨噬细胞之间的相互作用尚不清楚。在本研究中，我们证明了环化酶结合蛋白2（CAP2）在GC中上调表达，尤其在淋巴结转移的病例中，并与预后较差相关。转录因子JUN直接结合到CAP2的启动子区域并激活CAP2的转录。CAP2的N端结域与活化C激酶受体1（RACK1）的WD5-7结域结合，并通过激活SRC/ focal adhesion kinase（FAK）/ ERK信号通路诱导M2型巨噬细胞极化，进而促进白介素-4（IL4）和白介素-10（IL10）的分泌。极化的M2型巨噬细胞通过分泌转化生长因子β（TGFB1）诱导前转移信号Niche的形成并促进GC的转移，从而形成了TGFB1/JUN/CAP2正反馈环路以持续激活CAP2的表达。此外，我们发现丹酚酸B是CAP2的一种抑制剂，通过抑制SRC/FAK/ERK信号通路，有效地抑制GC细胞的侵袭能力。我们的数据表明，CAP2是介导GC细胞与肿瘤相关巨噬细胞相互作用的关键分子，可能是GC中抑制肿瘤转移的有希望的治疗靶点。

The metastasis of cancer cells is the main cause of death for patients with gastric cancer (GC). Mounting evidence has demonstrated the vital importance of tumor-associated macrophages in promoting tumor invasion and metastasis; however, the interaction between tumor cells and macrophages in GC is largely unknown. In this study, we demonstrated that cyclase-associated protein 2 (CAP2) was upregulated in GC, especially in cases with lymph node metastasis, and was correlated with a poorer prognosis. The transcription factor JUN directly bound to the promoter region of CAP2 and activated CAP2 transcription. The N-terminal domain of CAP2 bound to the WD5-7 domain of receptor for activated C kinase 1 (RACK1) and induced M2 macrophage polarization by activating the SRC/focal adhesion kinase (FAK)/ ERK signaling pathway, which resulted in interleukin-4 (IL4) and IL10 secretion. Polarized M2 macrophages induced premetastatic niche formation and promoted GC metastasis by secreting transforming growth factor beta (TGFB1), which created a TGFB1/JUN/CAP2-positive feedback loop to activate CAP2 expression continuously. Furthermore, we identified Salvianolic acid B as an inhibitor of CAP2, which effectively inhibited GC cell invasion capabilities by suppressing the SRC/FAK/ERK signaling pathway. Our data suggest that CAP2, a key molecule mediating the interaction between GC cells and tumor-associated macrophages, may be a promising therapeutic target for suppressing tumor metastasis in GC.