Buensuceso Adrian, Borrelli Matthew J, Ramos Valdés Yudith, Shepherd Trevor G
The Mary & John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON, Canada.
Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
Cancer Gene Ther. 2025 Jan;32(1):83-94. doi: 10.1038/s41417-024-00850-z. Epub 2024 Nov 21.
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.
从原发性肿瘤脱离后，上皮性卵巢癌细胞可形成多细胞聚集体，也称为球体，这些球体有能力在远处部位形成转移灶。这些结构表现出许多适应性变化，可能有助于转移过程并促进致瘤潜能。其中一种适应性变化是获得休眠状态，其特征是增殖减少和静止的分子特征。癌症中最常失调的基因之一是MYC，它编码一种促进细胞增殖的转录因子。在本研究中，我们证明与贴壁细胞相比，EOC球体中MYC蛋白丰度和相关基因表达显著降低。这种下调在细胞脱离后迅速发生，且依赖蛋白酶体。此外，当球体重新附着于贴壁培养表面时，MYC蛋白丰度和相关基因表达得以恢复。总体而言，我们的研究结果表明，MYC活性的抑制是EOC球体的一个共同特征，可能有助于休眠状态的可逆获得。
