Dynamic Change in p63 Protein Expression during Implantation of Urothelial Cancer Clusters.
Dynamic Change in p63 Protein Expression during Implantation of Urothelial Cancer Clusters.
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DOI：
10.1016/j.neo.2015.07.004
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Inoue M
中科院分区：
文献类型：
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作者：
Yoshida T;Okuyama H;Nakayama M;Endo H;Tomita Y;Nonomura N;Nishimura K;Inoue M
虽然尿路上皮癌细胞的播散被认为是尿路上皮肿瘤多中心的主要原因，但其种植机制尚未得到很好的研究。在这里，我们发现来自尿路上皮癌患者尿液的癌细胞簇保留了存活、生长和粘附的能力。通过使用从多个患者收集的细胞系和原代细胞，我们证明，当癌细胞簇附着到基质时，癌细胞簇中的△ Np 63 α蛋白通过蛋白酶体降解迅速减少，导致E-cadherin下调和N-cadherin上调。尿路上皮癌细胞团中△ Np 63 α蛋白水平的降低参与了尿路上皮癌的清除。我们的数据提供了第一个证据，表明尿路上皮癌细胞簇在附着于基质过程中表现出△ Np 63 α表达的动态变化，并且△ Np 63 α蛋白的降低在癌细胞簇与尿路上皮细胞之间的相互作用中起关键作用。因此，由于△ Np 63 α可能参与尿路上皮癌细胞的腔内扩散过程，因此阻断△ Np 63 α的降解可能是预防尿路上皮癌扩散的治疗靶点。
Although the dissemination of urothelial cancer cells is supposed to be a major cause of the multicentricity of urothelial tumors, the mechanism of implantation has not been well investigated. Here, we found that cancer cell clusters from the urine of patients with urothelial cancer retain the ability to survive, grow, and adhere. By using cell lines and primary cells collected from multiple patients, we demonstrate that △ Np63α protein in cancer cell clusters was rapidly decreased through proteasomal degradation when clusters were attached to the matrix, leading to downregulation of E-cadherin and upregulation of N-cadherin. Decreased △ Np63α protein level in urothelial cancer cell clusters was involved in the clearance of the urothelium. Our data provide the first evidence that clusters of urothelial cancer cells exhibit dynamic changes in △ Np63α expression during attachment to the matrix, and decreased △ Np63α protein plays a critical role in the interaction between cancer cell clusters and the urothelium. Thus, because △ Np63α might be involved in the process of intraluminal dissemination of urothelial cancer cells, blocking the degradation of △ Np63α could be a target of therapy to prevent the dissemination of urothelial cancer.