在转移性上皮性卵巢癌球状体模型中MYC的可逆性下调
Reversible downregulation of MYC in a spheroid model of metastatic epithelial ovarian cancer
原文发布日期:2024-11-21
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Upon detachment from the primary tumour, epithelial ovarian cancer cells can form multicellular aggregates, also referred to as spheroids, that have the capacity to establish metastases at distant sites. These structures exhibit numerous adaptations that may facilitate metastatic transit and promote tumorigenic potential. One such adaptation is the acquisition of dormancy, characterized by decreased proliferation and molecular features of quiescence. One of the most frequently dysregulated genes in cancer is MYC, which encodes a transcription factor that promotes cell proliferation. In this study, we demonstrate that MYC protein abundance and associated gene expression is significantly decreased in EOC spheroids compared to adherent cells. This downregulation occurs rapidly upon cell detachment and is proteasome-dependent. Moreover, MYC protein abundance and associated gene expression is restored upon spheroid reattachment to an adherent culture surface. Overall, our findings suggest that suppression of MYC activity is a common feature of EOC spheroids and may contribute to the reversible acquisition of dormancy.
从原发肿瘤脱落后,上皮性卵巢癌细胞可形成多细胞聚集体(亦称为球状体),这些聚集体能够在远端部位形成转移灶。此类结构表现出多种适应性改变,可能促进转移过程并增强致瘤潜能。其中一种适应性变化是获得休眠特性,表现为增殖能力下降并呈现分子水平的静息状态。MYC作为癌症中最常失调的基因之一,其编码的转录因子可促进细胞增殖。本研究表明,与贴壁细胞相比,上皮性卵巢癌球状体中MYC蛋白丰度及相关基因表达显著降低。这种下调现象在细胞脱落后迅速发生,且具有蛋白酶体依赖性。更重要的是,当球状体重新贴附于培养表面后,MYC蛋白丰度及相关基因表达得以恢复。总体而言,我们的研究结果表明MYC活性抑制是上皮性卵巢癌球状体的共同特征,这可能有助于细胞可逆性地获得休眠状态。
Reversible downregulation of MYC in a spheroid model of metastatic epithelial ovarian cancer
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