研究动态
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Kras 突变癌症中不存在应激颗粒,并且不能控制肿瘤生长。

Stress granules are not present in Kras mutant cancers and do not control tumor growth.

发表日期:2024 Oct 10
作者: Maxime Libert, Sophie Quiquempoix, Jean S Fain, Sébastien Pyr Dit Ruys, Malak Haidar, Margaux Wulleman, Gaëtan Herinckx, Didier Vertommen, Christelle Bouchart, Tatjana Arsenijevic, Jean-Luc Van Laethem, Patrick Jacquemin
来源: EMBO REPORTS

摘要:

应激颗粒 (SG) 是基于核糖核蛋白的无膜细胞质细胞器,可响应应激而组装。它们的形成通常与几乎整体的翻译抑制有关,并且这些颗粒的异常组装或分解对神经变性和癌症具有病理学意义。在癌症中,特别是在存在致癌 KRAS 突变的情况下,体内研究得出结论,SG 可以提高癌细胞对应激的抵抗力。因此,SG 最近被认为是一个有前途的治疗靶点。在这里,从我们观察到编码 SG 蛋白的基因在胰腺导管腺癌的发展过程中受到刺激开始,我们分析了肿瘤发生过程中 SG 的形成。我们利用小鼠模型、人体样本和人体数据,采用体外、体内和计算机方法。我们的分析不支持 SG 是在 KRAS 驱动的癌症的肿瘤发生过程中形成的,至少它们的存在并不普遍,因此我们建议在考虑 SG 作为治疗靶点之前需要谨慎。© 2024。作者。
Stress granules (SG) are membraneless ribonucleoprotein-based cytoplasmic organelles that assemble in response to stress. Their formation is often associated with an almost global suppression of translation, and the aberrant assembly or disassembly of these granules has pathological implications in neurodegeneration and cancer. In cancer, and particularly in the presence of oncogenic KRAS mutations, in vivo studies concluded that SG increase the resistance of cancer cells to stress. Hence, SG have recently been considered a promising target for therapy. Here, starting from our observations that genes coding for SG proteins are stimulated during development of pancreatic ductal adenocarcinoma, we analyze the formation of SG during tumorigenesis. We resort to in vitro, in vivo and in silico approaches, using mouse models, human samples and human data. Our analyses do not support that SG are formed during tumorigenesis of KRAS-driven cancers, at least that their presence is not universal, leading us to propose that caution is required before considering SG as therapeutic targets.© 2024. The Author(s).