YAP1 modulation of primary cilia-mediated ciliogenesis in 2D and 3D prostate cancer models.

IF 3.5 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology FEBS Letters Pub Date : 2024-12-01 Epub Date: 2024-10-18 DOI:10.1002/1873-3468.15029
Yingbo Guo, Mathilde Dupart, Marie Irondelle, Pascal Peraldi, Frederic Bost, Nathalie M Mazure
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Abstract

The primary cilium, a non-motile organelle present in most human cells, plays a crucial role in detecting microenvironmental changes and regulating intracellular signaling. Its dysfunction is linked to various diseases, including cancer. We explored the role of ciliated cells in prostate cancer by using Gefitinib and Jasplakinolide compounds to induce ciliated cells in both normal and tumor-like prostate cell lines. We assessed GLI1 and IFT20 expression and investigated YAP1 protein's role, which is implicated in primary cilium regulation. Finally, we examined these compounds in 3D cell models, aiming to simulate in vivo conditions. Our study highlights YAP1 as a potential target for novel genetic models to understand the primary cilium's role in mediating resistance to anticancer treatments.

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YAP1 在二维和三维前列腺癌模型中对原发性纤毛介导的纤毛生成的调节。
初级纤毛是存在于大多数人类细胞中的一种非运动细胞器,在检测微环境变化和调节细胞内信号传导方面发挥着至关重要的作用。它的功能障碍与包括癌症在内的多种疾病有关。我们利用吉非替尼(Gefitinib)和雅斯普利内酯(Jasplakinolide)化合物诱导正常和肿瘤样前列腺细胞系中的纤毛细胞,探讨了纤毛细胞在前列腺癌中的作用。我们评估了 GLI1 和 IFT20 的表达,并研究了 YAP1 蛋白的作用,该蛋白与原发性纤毛调节有关。最后,我们在三维细胞模型中检测了这些化合物,旨在模拟体内条件。我们的研究强调,YAP1 是新型遗传模型的潜在靶点,可用于了解原发性纤毛在介导抗癌治疗耐药性方面的作用。
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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
7.00
自引率
2.90%
发文量
303
审稿时长
1.0 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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