Caveolin-1 (Cav-1) 是一种关键的脂筏蛋白，具有肿瘤抑制因子和促进剂的双重作用。虽然它在肿瘤发生、进展和转移中的作用已被认识，但 Cav-1 对原发性乳腺恶性肿瘤肺转移发生的明确贡献仍不清楚。在这里，我们提出了第一个证据，表明乳腺上皮细胞中的 Cav-1 敲除可显着减少同基因乳腺癌小鼠模型中的肺转移。在体外，与对照组相比，4T1 细胞中的 Cav-1 敲除抑制了细胞外囊泡分泌、细胞运动和 MMP 分泌。作为补充，体内分析表明，与野生型细胞相比，注射 Cav-1 敲除 4T1 细胞的小鼠肺转移灶显着减少，原发肿瘤的 mRNA 分析进一步证实了这一点。我们鉴定了 21 个上皮细胞迁移基因，它们在源自 Cav-1 敲除细胞和野生型 4T1 细胞的肿瘤中表现出不同的表达。相关分析和免疫印迹进一步表明，Cav-1可能通过整合素α3（ITGα3）调节转移。计算机蛋白对接预测了 Cav-1 和 ITGα3 之间的相互作用，并通过免疫共沉淀证实了这一点。此外，Cav-1 和 ITGα3 敲低在细胞迁移测定中证实了其在转移中的作用。© 2024。作者。

Caveolin-1 (Cav-1) is a critical lipid raft protein playing dual roles as both a tumor suppressor and promoter. While its role in tumorigenesis, progression, and metastasis has been recognized, the explicit contribution of Cav-1 to the onset of lung metastasis from primary breast malignancies remains unclear. Here, we present the first evidence that Cav-1 knockout in mammary epithelial cells significantly reduces lung metastasis in syngeneic breast cancer mouse models. In vitro, Cav-1 knockout in 4T1 cells suppressed extracellular vesicle secretion, cellular motility, and MMP secretion compared to controls. Complementing this, in vivo analyses demonstrated a marked reduction in lung metastatic foci in mice injected with Cav-1 knockout 4T1 cells as compared to wild-type cells, which was further corroborated by mRNA profiling of the primary tumor. We identified 21 epithelial cell migration genes exhibiting varied expression in tumors derived from Cav-1 knockout and wild-type 4T1 cells. Correlation analysis and immunoblotting further revealed that Cav-1 might regulate metastasis via integrin α3 (ITGα3). In silico protein docking predicted an interaction between Cav-1 and ITGα3, which was confirmed by co-immunoprecipitation. Furthermore, Cav-1 and ITGα3 knockdown corroborated its role in metastasis in the cell migration assay.© 2024. The Author(s).