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核糖体功能不足与癌症增加并存的悖论:将视角从癌细胞转向微环境

The Paradox of Ribosomal Insufficiency Coupled with Increased Cancer: Shifting the Perspective from the Cancer Cell to the Microenvironment.

作者信息

D'Andrea Giacomo, Deroma Giorgia, Miluzio Annarita, Biffo Stefano

机构信息

National Institute of Molecular Genetics, INGM Fondazione Romeo ed Enrica Invernizzi, 20122 Milan, Italy.

Department of Biosciences, University of Milan, 20133 Milan, Italy.

出版信息

Cancers (Basel). 2024 Jun 28;16(13):2392. doi: 10.3390/cancers16132392.

Abstract

Ribosomopathies are defined as inherited diseases in which ribosomal factors are mutated. In general, they present multiorgan symptoms. In spite of the fact that in cellular models, ribosomal insufficiency leads to a reduced rate of oncogenic transformation, patients affected by ribosomopathies present a paradoxical increase in cancer incidence. Several hypotheses that explain this paradox have been formulated, mostly on the assumption that altered ribosomes in a stem cell induce compensatory changes that lead to a cancer cell. For instance, the lack of a specific ribosomal protein can lead to the generation of an abnormal ribosome, an oncoribosome, that itself leads to altered translation and increased tumorigenesis. Alternatively, the presence of ribosomal stress may induce compensatory proliferation that in turns selects the loss of tumor suppressors such as p53. However, modern views on cancer have shifted the focus from the cancer cell to the tumor microenvironment. In particular, it is evident that human lymphocytes are able to eliminate mutant cells and contribute to the maintenance of cancer-free tissues. Indeed, many tumors develop in conditions of reduced immune surveillance. In this review, we summarize the current evidence and attempt to explain cancer and ribosomopathies from the perspective of the microenvironment.

摘要

核糖体病被定义为核糖体因子发生突变的遗传性疾病。一般来说,它们会出现多器官症状。尽管在细胞模型中,核糖体功能不足会导致致癌转化速率降低,但患核糖体病的患者癌症发病率却反常增加。已经提出了几种解释这种矛盾现象的假说,大多基于这样的假设:干细胞中核糖体的改变会引发补偿性变化,从而导致癌细胞的产生。例如,缺乏特定的核糖体蛋白会导致异常核糖体(即癌核糖体)的产生,而这种异常核糖体本身会导致翻译改变并增加肿瘤发生。或者,核糖体应激的存在可能会诱导补偿性增殖,进而导致肿瘤抑制因子(如p53)的缺失。然而,现代癌症观点已将焦点从癌细胞转移到了肿瘤微环境。特别是,很明显人类淋巴细胞能够清除突变细胞并有助于维持无癌组织。事实上,许多肿瘤是在免疫监视减弱的情况下发生的。在这篇综述中,我们总结了当前的证据,并试图从微环境的角度解释癌症和核糖体病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2831/11240629/d89c622a10fb/cancers-16-02392-g001.jpg

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