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机械感知通道 PIEZO2 增强三阴性乳腺癌的侵袭表型。

Mechano-Sensing Channel PIEZO2 Enhances Invasive Phenotype in Triple-Negative Breast Cancer.

机构信息

Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, The State University of New York, Buffalo, NY 14203, USA.

出版信息

Int J Mol Sci. 2022 Aug 31;23(17):9909. doi: 10.3390/ijms23179909.

DOI:10.3390/ijms23179909
PMID:36077309
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9455988/
Abstract

BACKGROUND

Mechanically gated PIEZO channels lead to an influx of cations, activation of additional Ca channels, and cell depolarization. This study aimed to investigate PIEZO2's role in breast cancer.

METHODS

The clinical relevance of expression in breast cancer patient was analyzed in a publicly available dataset. Utilizing overexpressed breast cancer cells, and and experiments were conducted.

RESULTS

High expression of was correlated with a worse survival in triple-negative breast cancer (TNBC) but not in other subtypes. Increased PEIZO2 channel function was confirmed in overexpressed cells after mechanical stimulation. overexpressed cells showed increased motility and invasive phenotypes as well as higher expression of SNAIL and Vimentin and lower expression of E-cadherin in TNBC cells. Correspondingly, high expression of was correlated with the increased expression of epithelial-mesenchymal transition (EMT)-related genes in a TNBC patient. Activated Akt signaling was observed in overexpressed TNBC cells. overexpressed MDA-MB-231 cells formed a significantly higher number of lung metastases after orthotopic implantation.

CONCLUSION

PIEZO2 activation led to enhanced SNAIL stabilization through Akt activation. It enhanced Vimentin and repressed E-cadherin transcription, resulting in increased metastatic potential and poor clinical outcomes in TNBC patients.

摘要

背景

机械门控 PIEZO 通道导致阳离子内流、其他 Ca 通道激活和细胞去极化。本研究旨在探讨 PIEZO2 在乳腺癌中的作用。

方法

在一个公开的可用数据集分析 在乳腺癌患者中的临床相关性。利用 过表达的乳腺癌细胞进行 和 实验。

结果

高表达 与三阴性乳腺癌（TNBC）患者的生存率较差相关，但与其他亚型无关。机械刺激后证实 过表达细胞中 PEIZO2 通道功能增加。 过表达细胞表现出更高的迁移和侵袭表型，以及更高的 SNAIL 和 Vimentin 表达和更低的 E-cadherin 表达在 TNBC 细胞中。相应地，在 TNBC 患者中， 的高表达与上皮-间充质转化（EMT）相关基因的表达增加相关。在 过表达的 TNBC 细胞中观察到激活的 Akt 信号。 过表达的 MDA-MB-231 细胞在原位植入后形成了明显更多的肺转移。

结论

PIEZO2 激活通过 Akt 激活导致 SNAIL 稳定性增强。它增强了 Vimentin 并抑制了 E-cadherin 的转录，从而增加了 TNBC 患者的转移潜力和不良临床结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/298e/9455988/cb4f1a6a467e/ijms-23-09909-g007.jpg
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