Plasminogen activator inhibitor (PAI) trap3, an exocellular peptide inhibitor of PAI-1, attenuates the rearrangement of F-actin and migration of cancer cells
Plasminogen activator inhibitor (PAI) trap3, an exocellular peptide inhibitor of PAI-1, attenuates the rearrangement of F-actin and migration of cancer cells
复制标题
纤溶酶原激活剂抑制剂 (PAI) trap3 是一种 PAI-1 的胞外肽抑制剂，可减弱 F-肌动蛋白的重排和癌细胞的迁移
DOI：
10.1016/j.yexcr.2020.111987
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发表时间：
2020-06-01
影响因子：
3.7
通讯作者：
Zhang, Lei
中科院分区：
文献类型：
--
作者：
Liu, Jihao;Chen, Zhuo;Zhang, Lei
背景：蛋白纤溶酶原激活物抑制物-1(PAI-1)是尿激酶型纤溶酶原激活物(UPA)和组织型纤溶酶原激活物(TPA)的特异性抑制物，已被证明在肿瘤转移中起关键作用。方法：通过将突变的uPA丝氨酸蛋白酶结构域(SPD)与人血清白蛋白(HSA)融合，合成捕获PAI-1的蛋白PAItrap3，并通过体外实验观察PAItrap3能否抑制PAI-1诱导的癌细胞迁移。结果：细胞外PAItrap3(0.8mM)对MCF-7、MDA-MB-231、HeLa和4T1癌细胞的运动抑制作用分别为90%、50%、30%和20%，而对癌细胞的增殖无明显影响。PAItrap3可显著抑制PAI-1诱导的F-肌动蛋白重排，使细胞突起数减少至少20%。结论：PAItrap3体外抑制PAI-1诱导的癌细胞迁移，主要是通过抑制F-肌动蛋白重排实现的。总体而言，这些结果，如果它们可以外推到人类，表明PAItrap3蛋白可以用作细胞外抑制物，以减少癌症转移。
Background: The protein plasminogen activator inhibitor-1 (PAI-1), an inhibitor specific for urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA), has been shown to have a key role in cancer metastases. Currently, it is unknown as to whether the exocellular inhibition of PAI-1 can inhibit the migration of cancer cells.Methods: By fusing the mutated serine protease domain (SPD) of uPA and human serum albumin (HSA), PAItrap3, a protein that traps PAI-1, was synthesized and experiments were conducted to determine if exocellular PAItrap3 attenuates PAI-1-induced cancer cell migration in vitro.Results: PAItrap3 (0.8 mu M) significantly inhibited the motility of MCF-7, MDA-MB-231, HeLa and 4T1 cancer cells, by 90%, 50%, 30% and 20%, respectively, without significantly altering their proliferation. The PAI-1-induced rearrangement of F-actin was significantly inhibited by PAItrap3, which produced a decrease in the number of cell protrusions by at least 20%.Conclusions: In vitro, PAItrap3 inhibited PAI-1-induced cancer cell migration, mainly through inhibiting the rearrangement of F-actin. Overall, these results, provided they can be extrapolated to humans, suggest that the PAItrap3 protein could be used as an exocellular inhibitor to attenuate cancer metastases.