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ΔNp63α promotes adhesion of metastatic prostate cancer cells to the bone through regulation of CD82

机译:ΔNp63α通过调节CD82促进转移性前列腺癌细胞与骨骼的粘附

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摘要

ΔNp63α is a critical mediator of epithelial development and stem cell function in a variety of tissues including the skin and breast, while overexpression of ΔNp63α acts as an oncogene to drive tumor formation and cancer stem cell properties in squamous cell carcinoma. However, with regards to the prostate, while ΔNp63α is expressed in the basal stem cells of the mature gland, during adenocarcinoma development, its expression is lost and its absence is used to clinically diagnose the malignant state. Surprisingly, here we identify a sub-population of bone metastatic prostate cancer cells in the PC3 cell line that express ΔNp63α. Interestingly, we discovered that ΔNp63α favors adhesion and stem-like growth of these cells in the bone microenvironment. In addition, we show that these properties require expression of the target gene CD82. Together, this work uncovers a population of bone metastatic prostate cancer cells that express ΔNp63α, and provides important information about the mechanisms of bone metastatic colonization. Finally, we identify metastasis-promoting properties for the tetraspanin family member CD82.
机译:ΔNp63α是包括皮肤和乳房在内的多种组织中上皮发育和干细胞功能的关键介体,而ΔNp63α的过表达则是癌基因,可驱动鳞状细胞癌的肿瘤形成和癌干细胞特性。然而,对于前列腺而言,尽管ΔNp63α在成熟腺的基底干细胞中表达,但是在腺癌发生过程中,其表达丢失并且其缺失被用于临床诊断恶性状态。出人意料的是,我们在PC3细胞系中鉴定出表达ΔNp63α的骨转移性前列腺癌细胞亚群。有趣的是,我们发现ΔNp63α有利于这些细胞在骨骼微环境中的粘附和茎状生长。此外,我们表明这些属性需要目标基因CD82的表达。这项工作共同发现了表达ΔNp63α的骨转移性前列腺癌细胞,并提供了有关骨转移定植机制的重要信息。最后,我们确定了四跨膜家族成员CD82的转移促进特性。

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