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肌动蛋白运动蛋白肌球蛋白6促进乳腺癌细胞的迁移以及GIPC1和septins的表达。

The Actin Motor Protein Myosin 6 Contributes to Cell Migration and Expression of GIPC1 and Septins in Breast Cancer Cells.

作者信息

Izdebska Magdalena, Arendt Wioletta, Hałas-Wiśniewska Marta, Zakrzewski Przemysław, Lenartowski Robert, Lenartowska Marta

机构信息

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

School of Cellular and Molecular Medicine, Faculty of Life Sciences, University of Bristol, University Walk, Bristol, UK.

出版信息

Cancer Manag Res. 2024 Oct 19;16:1445-1462. doi: 10.2147/CMAR.S479151. eCollection 2024.

DOI:10.2147/CMAR.S479151
PMID:39445095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11498146/
Abstract

INTRODUCTION

Breast cancer is highly metastatic. One protein that may participate in breast cancer cell migration is the actin motor protein myosin 6 (MYO6), which is likely regulated by the GIPC1 protein. Additionally, septins (SEPTs) appear to participate in breast cancer motility. Here, we investigated the effects of loss of MYO6 on cell morphology, migration, and expression of GIPC1, SEPT2, and SEPT7 in two breast cancer cell lines.

MATERIAL AND METHODS

The research material consisted of two breast cancer cell lines, MCF-7 and MDA-MB-231, in which the level of MYO6 was reduced and the effect of knockdown on the migration potential and the expression of GIPC1, SEPT2 and SEPT7 was determined. The levels of these proteins were also analyzed in silico.

RESULTS

siRNA-mediated knock down of MYO6 altered the morphology of MCF-7 cells and reduced the expression of GIPC1 and SEPT7 in both MCF-7 and MDA-MB-231 cells. In in silico data, GIPC1, SEPT2, and SEPT7 were all overexpressed in breast cancer tissue samples from patients. Finally, MYO6 knock down impaired migration and adhesion in both MCF-7 and MDA-MB-231 cells.

CONCLUSION

Our study substantiates that downregulation of MYO6 diminishes the migratory abilities of breast cancer cell lines with varying invasiveness. Furthermore, we have demonstrated that decreased MYO6 protein leads to reduced expression of GIPC1, SEPT2, and SEPT7 in breast cancer cells. These findings contribute to a more comprehensive understanding of the pathways influencing breast cancer cell migration, a critical aspect of metastasis.

摘要

引言

乳腺癌具有高度转移性。一种可能参与乳腺癌细胞迁移的蛋白质是肌动蛋白运动蛋白肌球蛋白6(MYO6),它可能受GIPC1蛋白调控。此外,septins(SEPTs)似乎也参与乳腺癌的运动。在此,我们研究了MYO6缺失对两种乳腺癌细胞系的细胞形态、迁移以及GIPC1、SEPT2和SEPT7表达的影响。

材料与方法

研究材料包括两种乳腺癌细胞系MCF - 7和MDA - MB - 231,其中MYO6水平降低,并确定敲低对迁移潜能以及GIPC1、SEPT2和SEPT7表达的影响。还通过计算机分析这些蛋白质的水平。

结果

siRNA介导的MYO6敲低改变了MCF - 7细胞的形态,并降低了MCF - 7和MDA - MB - 231细胞中GIPC1和SEPT7的表达。在计算机分析数据中,GIPC1、SEPT2和SEPT7在患者的乳腺癌组织样本中均过度表达。最后,MYO6敲低损害了MCF - 7和MDA - MB - 231细胞的迁移和黏附。

结论

我们的研究证实,MYO6的下调会降低具有不同侵袭性的乳腺癌细胞系的迁移能力。此外,我们证明了乳腺癌细胞中MYO6蛋白减少会导致GIPC1、SEPT2和SEPT7的表达降低。这些发现有助于更全面地理解影响乳腺癌细胞迁移的途径,而这是转移的一个关键方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0b/11498146/af521796e5c9/CMAR-16-1445-g0012.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0b/11498146/77c6592a0ab0/CMAR-16-1445-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0b/11498146/190e14e94353/CMAR-16-1445-g0005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0b/11498146/a4023c210f5e/CMAR-16-1445-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0b/11498146/3151ce971c7d/CMAR-16-1445-g0009.jpg
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本文引用的文献

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A comprehensive analysis of MYO6 as a promising biomarker for diagnosis, prognosis, and immunity in clear cell renal cell carcinoma.对MYO6作为透明细胞肾细胞癌诊断、预后和免疫的有前景生物标志物的综合分析。
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Elevated expression of myosin VI contributes to breast cancer progression via MAPK/ERK signaling pathway.
肌球蛋白VI的高表达通过MAPK/ERK信号通路促进乳腺癌进展。
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Multimodal regulation of myosin VI ensemble transport by cargo adaptor protein GIPC.货物衔接蛋白 GIPC 对肌球蛋白 VI 整体运输的多模式调控。
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Visualizing and interpreting cancer genomics data via the Xena platform.通过Xena平台可视化和解读癌症基因组学数据。
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Are 90% of deaths from cancer caused by metastases?癌症导致的死亡中,90%是由转移引起的吗?
Cancer Med. 2019 Sep;8(12):5574-5576. doi: 10.1002/cam4.2474. Epub 2019 Aug 8.
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Downregulation of myosin VI reduced cell growth and increased apoptosis in human colorectal cancer.肌球蛋白VI的下调可降低人结直肠癌的细胞生长并增加细胞凋亡。
Acta Biochim Biophys Sin (Shanghai). 2018 Jul 1;50(7):731. doi: 10.1093/abbs/gmy035.
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The MYO6 interactome reveals adaptor complexes coordinating early endosome and cytoskeletal dynamics.MYO6 相互作用组揭示了衔接复合物协调早期内体和细胞骨架动态的作用。
EMBO Rep. 2018 Apr;19(4). doi: 10.15252/embr.201744884. Epub 2018 Feb 21.
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10
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