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FHOD1的下调抑制A549细胞的转移潜能。

Downregulation of FHOD1 Inhibits Metastatic Potential in A549 Cells.

作者信息

Hałas-Wiśniewska Marta, Izdebska Magdalena, Zielińska Wioletta, Grzanka Alina

机构信息

Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Bydgoszcz 85-092, Poland.

出版信息

Cancer Manag Res. 2021 Jan 8;13:91-106. doi: 10.2147/CMAR.S286239. eCollection 2021.

Abstract

PURPOSE

Metastasis remains a serious clinical problem in which epithelial-to-mesenchymal transition is strictly involved. The change of cell phenotype is closely related to the dynamics of the cytoskeleton. Regarding the great interest in microfilaments, the manipulation of ABPs (actin-binding proteins) appears to be an interesting treatment strategy.

MATERIAL

The research material was the highly aggressive A549 cells with FHOD1 (F FH1/FH2 domain-containing protein 1) downregulation. The metastatic potential of the cells and the sensitivity to treatment with alkaloids (piperlongumine, sanguinarine) were analyzed.

RESULTS

In comparison to A549 cells with naïve expression of FHOD1, those after manipulation were characterized by a reduced migratory potential. The obtained results were associated with microfilaments and vimentin reorganization induced by the manipulation of FHOD1 together with alkaloids treatment. The result was also an increase in the percentage of late apoptotic cells.

CONCLUSION

Downregulation of FHOD1 induced reorganization of microfilament network followed by the reduction in the metastatic potential of the A549 cells, as well as their sensitization to selected compounds. The presented results and the analysis of clinical data indicate the possibility of transferring research from the basic level to in vivo models in the context of manipulation of ABPs as a new therapeutic target in oncology.

摘要

目的

转移仍然是一个严重的临床问题,上皮-间质转化在其中起着关键作用。细胞表型的变化与细胞骨架的动态变化密切相关。鉴于对微丝的高度关注,对肌动蛋白结合蛋白(ABP)的操控似乎是一种有趣的治疗策略。

材料

研究材料是FHOD1(含FH1/FH2结构域蛋白1)下调的高侵袭性A549细胞。分析了细胞的转移潜能以及对生物碱(胡椒碱、血根碱)治疗的敏感性。

结果

与FHOD1天然表达的A549细胞相比,操控后的细胞迁移潜能降低。所得结果与FHOD1操控及生物碱处理诱导的微丝和波形蛋白重组有关。结果还显示晚期凋亡细胞的百分比增加。

结论

FHOD1下调诱导微丝网络重组,随后A549细胞的转移潜能降低,并使其对所选化合物敏感。所呈现的结果以及临床数据分析表明,在将ABP作为肿瘤学新治疗靶点进行操控的背景下,有可能将基础研究成果转化为体内模型研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e77/7802784/540b2db8a44f/CMAR-13-91-g0001.jpg

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