Fibronectin-containing High-Density Lipoprotein is Associated with Cancer Cell Adhesion and Proliferation.
Fibronectin-containing High-Density Lipoprotein is Associated with Cancer Cell Adhesion and Proliferation.
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发表时间：
2020-08
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通讯作者：
Eriko Hisamatsu;M. Nagao;R. Toh;Y. Irino;T. Iino;T. Hara;Hidekazu Tanaka;S. Satomi-Kobayashi;T. Ishida;K. Hirata
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作者：
Eriko Hisamatsu;M. Nagao;R. Toh;Y. Irino;T. Iino;T. Hara;Hidekazu Tanaka;S. Satomi-Kobayashi;T. Ishida;K. Hirata
大量证据表明，高密度脂蛋白（HDL）具有抗动脉粥样硬化的特性。HDL-胆固醇（HDL-C）也被广泛用作心血管疾病的标志物。最近，据报道，血浆HDL-C水平与癌症风险呈负相关。然而，HDL和癌症病理生理学之间的关系仍然未知。在这里，我们试图研究HDL对癌症进展的影响。首先，我们专注于纤连蛋白-一种必需的细胞外基质糖蛋白-作为HDL相关蛋白，并发现在这项研究中只有7.4%的受试者从血浆中分离出HDL中的纤连蛋白。与不含纤连蛋白的HDL相比，含纤连蛋白的HDL（FN-HDL）增加了HeLa细胞中粘着斑激酶（FAK）的磷酸化，进一步以剂量依赖性方式诱导磷酸化。其次，我们发现FN-HDL可激活FAK的磷酸化，而其上游效应物可阻断FN-HDL诱导的FAK磷酸化。最后，我们证明，FN-HDL促进癌细胞增殖和粘附相比，HDL没有纤连蛋白。我们的研究显示了FN-HDL通过FAK信号通路增强癌细胞增殖和粘附的可能机制。进一步研究HDL组分在肿瘤发生中的作用可能为癌症病理生理学提供新的见解。
A large amount of evidence suggests that high-density lipoprotein (HDL) has anti-atherosclerotic properties. HDL-cholesterol (HDL-C) has also been widely used as a marker of cardiovascular disease. Recently, it was reported that plasma HDL-C levels are inversely correlated with cancer risk. However, the relationship between HDL and cancer pathophysiology remains unknown. Here, we sought to investigate the effect of HDL on cancer progression. First, we focused on fibronectin-an essential extracellular matrix glycoprotein-as an HDL-associated protein and found that only 7.4% of subjects in this study had fibronectin in HDL isolated from their plasma. The fibronectin-containing HDL (FN-HDL) increased the phosphorylation of focal adhesion kinase (FAK) in HeLa cells compared to HDL without fibronectin, further inducing the phosphorylation in a dose-dependent manner. Second, we found that fibronectin-treated HDL activated the phosphorylation of FAK, and its upstream effector blocked the phosphorylation induced by FN-HDL. Finally, we demonstrated that FN-HDL promoted cancer cell proliferation and adhesion compared to HDL without fibronectin. Our study showed the possible mechanism by which FN-HDL enhanced cancer cell proliferation and adhesion via the FAK signaling pathway. Further investigation of the roles of HDL components in tumorigenesis might provide novel insight into cancer pathophysiology.