当癌细胞进入血液循环时，它们可以与血小板相互作用，增强其生存和转移能力。为了阐明其潜在机制，我们将转移性黑色素瘤和三阴性乳腺癌细胞与种属同源的血小板进行共培养。我们发现，共培养的癌细胞在循环中显示出更高的存活能力，在体外具有更强的细胞迁移、侵袭和结块形成能力，并在小鼠体内显示更多的肿瘤生成和转移。RNA测序分析显示，共培养的癌细胞的血浆饱和蛋白水平（SERPINE1）显著上调。SERPINE1的沉默逆转了共培养提升的癌细胞存活和转移表型。机制研究表明，共培养与血小板激活了TGFβ/Smad通路，诱导了癌细胞中SERPINE1的表达，其编码溶酶原激活酶抑制剂1（PAI-1）。PAI-1随后激活PI3K，增加AKTThr308和Bad的磷酸化，提高Bcl-2的表达，增强细胞在循环中的存活能力。此外，我们在转移性黑色素瘤和三阴性乳腺癌患者的转移性肿瘤中检测到更高水平的PAI-1，而在正常组织中则很少检测到。高水平的PAI-1与乳腺癌患者的总体生存时间缩短和疾病进展恶化有关。PAI-1可能作为检测和治疗转移性肿瘤细胞的潜在生物标志物。© 作者。

When cancer cells enter the bloodstream, they can interact with platelets to acquire stronger survival and metastatic abilities. To elucidate the underlying mechanisms, we cocultured metastatic melanoma and triple-negative breast cancer cells with species-homologous platelets. We found that cocultured cancer cells displayed higher viabilities in circulation, stronger capacities for cell migration, invasion, and colony formation in vitro, and more tumorigenesis and metastasis in mice. RNA sequencing analysis revealed that the level of serpin family E member 1 (SERPINE1) was significantly upregulated in cocultured cancer cells. Knockdown of SERPINE1 reversed the coculture-elevated survival and metastatic phenotypes of cancer cells. Mechanistic studies indicated that coculture with platelets activated the TGFβ/Smad pathway to induce SERPINE1 expression in cancer cells, which encodes plasminogen activator inhibitor 1 (PAI-1). PAI-1 then activated PI3K to increase the phosphorylation of AKTThr308 and Bad to elevate Bcl-2, which enhanced cell survival in circulation. Moreover, higher levels of PAI-1 were detected in metastatic tumors from melanoma and triple-negative breast cancer patients than in normal tissues, and high levels of PAI-1 were associated with a shorter overall survival time and worse disease progression in breast cancer. PAI-1 may act as a potential biomarker for detecting and treating metastatic tumor cells.© The author(s).