Autophagy Suppresses Invasiveness of Endometrial Cells through Reduction of Fascin-1.
Autophagy Suppresses Invasiveness of Endometrial Cells through Reduction of Fascin-1.
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自噬通过减少 Fascin-1 抑制子宫内膜细胞的侵袭
DOI：
10.1155/2018/8615435
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发表时间：
2018
影响因子：
--
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Luo X;Cheng W;Wang S;Chen Z;Tan J
自噬已被报道参与各种疾病的发展，如神经退行性疾病和代谢性疾病以及肿瘤。自噬激活剂和抑制剂也是这些疾病的潜在治疗剂。然而，自噬参与不同疾病的机制并不相同，自噬在子宫内膜异位症（EM）中的作用尚未阐明。本研究探讨了自噬在EM中的作用机制，旨在为通过靶向干预自噬来防治EM奠定理论基础。 我们使用RNA干扰片段靶向ATG 5，自噬激活剂雷帕霉素，自噬抑制剂3-MA或过表达的丝状伪足相关蛋白fascin-1，结合克隆形成试验，生长曲线，划痕试验，研究自噬对细胞生长，增殖和侵袭的影响。我们收集了20例EM临床病例的标本，并研究了自噬标志物LC 3-II、自噬底物p62和fascin-1的蛋白表达。 雷帕霉素能够抑制增生细胞系CRL-7566的增殖和集落形成，而自噬抑制剂3-MA以及干扰自噬相关基因ATG 5具有相反的效果。更重要的是，自噬激活剂雷帕霉素能够抑制丝状伪足在增生细胞中的生长，并且fascin-1的过表达恢复了雷帕霉素诱导的侵袭性降低。我们发现，自噬标志物LC 3-II的表达在临床EM标本中与对照组相比显著降低，而fascin-1和自噬底物p62的表达增加。 我们的研究结果表明，抑制自噬和fascin-1的外源性表达可能会促进子宫内膜细胞的侵袭性。作为推论，自噬代表了治疗EM的潜在靶点。
Autophagy has been reported to be involved in the development of various disorders such as neurodegenerative and metabolic diseases and tumors. Autophagy activators and inhibitors are also potential therapeutics for these diseases. However, the mechanism of autophagic involvement in different diseases is not the same, and the role of autophagy in endometriosis (EM) has not yet been elucidated. This research investigated the mechanism by which autophagy acts in EM, with the aim of establishing a theoretical basis for its prevention and treatment through the targeted interference with autophagy. We used an RNA interference fragment targeting ATG5, the autophagy activator rapamycin, and the autophagy inhibitor 3-MA or overexpression of filopodia-related protein fascin-1, in conjunction with clonogenic assays, growth curves, and scratch assay to investigate the influence of autophagy on cellular growth, proliferation, and invasiveness. We collected specimens from 20 clinical cases of EM and investigated the protein expression of the autophagic marker LC3-II, the autophagic substrate p62, and fascin-1. Rapamycin was able to inhibit the proliferation and colony formation of the endometriotic cell line CRL-7566, whereas the autophagy inhibitor 3-MA as well as the interference with the autophagy-related gene ATG5 had the opposite effect. More importantly, the autophagy activator rapamycin was able to inhibit the growth of filopodia in the endometriotic cells, and the overexpression of the fascin-1 restored the rapamycin-induced decrease of invasiveness. We found that the expression of the autophagy marker LC3-II was significantly reduced among the clinical EM specimens compared to the control group, while the expressions of fascin-1 and autophagic substrate p62 were increased. Our results indicate that the inhibition of autophagy and exogenous expression of fascin-1 may promote the invasiveness of endometrial cells. As a corollary, autophagy represents a potential target for the treatment of EM.
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DOI：
10.1158/1940-6207.capr-10-0387
发表时间：
2011-07
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
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通讯作者：
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DOI：
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影响因子：
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发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
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