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桥粒芯蛋白2（DSC2）和桥粒斑蛋白1（PKP1）的桥粒蛋白通过增加循环系统中的聚集形成来促进癌细胞的存活和转移。

Desmosomal proteins of DSC2 and PKP1 promote cancer cells survival and metastasis by increasing cluster formation in circulatory system.

作者信息

Li Koukou, Wu Renfei, Zhou Muya, Tong Haibo, Luo Kathy Q

机构信息

Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China.

Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macao SAR, China.

出版信息

Sci Adv. 2021 Oct;7(40):eabg7265. doi: 10.1126/sciadv.abg7265. Epub 2021 Sep 29.

DOI:10.1126/sciadv.abg7265
PMID:34586853
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8480931/
Abstract

To study how cancer cells can withstand fluid shear stress (SS), we isolated SS-resistant breast and lung cancer cells using a microfluidic circulatory system. These SS-resistant cells showed higher abilities to form clusters, survive in circulation, and metastasize in mice. These SS-resistant cells expressed 4.2- to 5.3-fold more desmocollin-2 (DSC2) and plakophilin-1 (PKP1) proteins. The high expression of DSC2 and PKP1 facilitated cancer cells to form clusters in circulation, and also activated PI3K/AKT/Bcl-2–mediated pathway to increase cell survival. The high levels of DSC2 and PKP1 are also important for maintaining high expression of vimentin, which stimulates fibronectin/integrin β/FAK/Src/MEK/ERK/ZEB1–mediated metastasis. Moreover, higher levels of DSC2 and PKP1 were detected in tumor samples from patients with breast and lung cancer, and their high expression was correlated with lower overall survival and worse disease progression. DSC2 and PKP1 may serve as new biomarkers for detecting and targeting metastatic circulating tumor cells.

摘要

为了研究癌细胞如何耐受流体剪切应力（SS），我们使用微流控循环系统分离出抗SS的乳腺癌和肺癌细胞。这些抗SS细胞在形成聚集体、在循环中存活以及在小鼠体内转移方面表现出更高的能力。这些抗SS细胞表达的桥粒芯蛋白-2（DSC2）和盘状球蛋白-1（PKP1）蛋白多4.2至5.3倍。DSC2和PKP1的高表达促进癌细胞在循环中形成聚集体，还激活PI3K/AKT/Bcl-2介导的通路以提高细胞存活率。DSC2和PKP1的高水平对于维持波形蛋白的高表达也很重要，波形蛋白可刺激纤连蛋白/整合素β/粘着斑激酶/原癌基因酪氨酸蛋白激酶Src/丝裂原活化蛋白激酶/细胞外信号调节激酶/锌指蛋白E-盒结合因子1介导的转移。此外，在乳腺癌和肺癌患者的肿瘤样本中检测到更高水平的DSC2和PKP1，它们的高表达与较低的总生存率和较差的疾病进展相关。DSC2和PKP1可能作为检测和靶向转移性循环肿瘤细胞的新生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/d460fb1c7a43/sciadv.abg7265-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/50d97daec9b7/sciadv.abg7265-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/121e7b6e222b/sciadv.abg7265-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/78a88f594e02/sciadv.abg7265-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/11432e1e22a2/sciadv.abg7265-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/d460fb1c7a43/sciadv.abg7265-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/50d97daec9b7/sciadv.abg7265-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/aad45b3e9bd7/sciadv.abg7265-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/039e33d0ddfe/sciadv.abg7265-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/cca5e1cf2a7d/sciadv.abg7265-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/2c8f0ccf05e3/sciadv.abg7265-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/a7222ecbec70/sciadv.abg7265-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/121e7b6e222b/sciadv.abg7265-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/78a88f594e02/sciadv.abg7265-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/11432e1e22a2/sciadv.abg7265-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7817/8480931/d460fb1c7a43/sciadv.abg7265-f10.jpg

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