F806 Suppresses the Invasion and Metastasis of Esophageal Squamous Cell Carcinoma via Downregulating F-Actin Assembly-Related Rho Family Proteins.

F806 Suppresses the Invasion and Metastasis of Esophageal Squamous Cell Carcinoma via Downregulating F-Actin Assembly-Related Rho Family Proteins.
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F806通过下调F-肌动蛋白组装相关Rho家族蛋白抑制食管鳞状细胞癌的侵袭和转移

DOI:
10.1155/2018/2049313
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发表时间:
2018
影响因子:
--
通讯作者:
Li EM
Li EM
中科院分区:
生物学3区
文献类型:
--
作者:
Xie L;Li LY;Zheng D;Xie YM;Xu XE;Tao LH;Liao LD;Xie YH;Cheng YW;Xu LY;Li EM

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侵袭和转移是食管鳞癌的重要病理和死亡过程。靶向两个癌症迁移阶段的新药将增加ESCC治疗的治疗选择并提高总生存率。一种新的天然大环内酯F806特异性地促进多种ESCC细胞的凋亡。但F806是否能抑制食管鳞癌细胞的转移还需进一步研究。在此,我们的数据表明,F806抑制动态F-actin组装,然后抑制ESCC细胞在体外的迁移和在体内的侵袭和转移。癌症迁移和肌动蛋白细胞骨架组装之间的相关性与F806防止桩蛋白聚集的能力一致,桩蛋白是通过结合到肌动蛋白丝末端形成粘着斑的必需蛋白。此外,F806下调了Rho家族蛋白细胞分裂周期42(CDC 42)、RAC家族小GT3 1(RAC 1)和RAS同源家族成员A(RHOA)的表达和活性。综上所述,这些结果表明,F806可以通过中断涉及F-actin的迁移组分的组装来抑制癌症侵袭和转移。
Invasion and metastasis are critical pathological and mortal processes in esophageal squamous cell carcinoma (ESCC). Novel drugs, targeting the two cancer migration stages, will augment the treatment options for ESCC therapy and improve overall survival. A novel natural macrolide F806 specifically promotes apoptosis of various ESCC cells. However, whether F806 can inhibit metastasis of ESCC cells needs further evaluation. Here, our data showed that F806 inhibits dynamic F-actin assembly and then suppresses the migration of ESCC cells in vitro and their invasion and metastasis in vivo. The correlation between cancer migration and actin cytoskeleton assembly was consistent with the ability of F806 to prevent the aggregation of Paxillin, an essential protein for focal adhesion formation through binding to the ends of actin filaments. Furthermore, F806 downregulated the expression and activity of the Rho family proteins cell division cycle 42 (CDC42), RAC family small GTPase 1 (RAC1), and RAS homolog family member A (RHOA). Taken together, these results suggest that F806 can suppress cancer invasion and metastasis via interrupting the assembly of migration components involving F-actin.
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