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癌症与细胞多型性解体:黏菌(一种社会性阿米巴虫)能教给我们什么。

Cancer and the breakdown of multicellularity: What Dictyostelium discoideum, a social amoeba, can teach us.

机构信息

Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

出版信息

Bioessays. 2021 Apr;43(4):e2000156. doi: 10.1002/bies.202000156. Epub 2021 Jan 14.

Abstract

Ancient pathways promoting unicellularity and multicellularity are associated with cancer, the former being pro-oncogenic and the latter acting to suppress oncogenesis. However, there are only a limited number of non-vertebrate models for studying these pathways. Here, we review Dictyostelium discoideum and describe how it can be used to understand these gene networks. D. discoideum has a unicellular and multicellular life cycle, making it possible to study orthologs of cancer-associated genes in both phases. During development, differentiated amoebae form a fruiting body composed of a mass of spores that are supported atop a stalk. A portion of the cells sacrifice themselves to become non-reproductive stalk cells. Cheating disrupts the principles of multicellularity, as cheater cells alter their cell fate to preferentially become spores. Importantly, D. discoideum has gene networks and several strategies for maintaining multicellularity. Therefore, D. discoideum can help us better understand how conserved genes and pathways involved in multicellularity also influence cancer development, potentially identifying new therapeutic avenues.

摘要

促进单细胞和多细胞形成的古老途径与癌症有关,前者致癌,后者抑制致癌。然而,用于研究这些途径的无脊椎动物模型数量有限。本文综述了盘基网柄菌,并描述了如何利用它来理解这些基因网络。盘基网柄菌具有单细胞和多细胞生命周期,因此可以在这两个阶段研究与癌症相关的基因的同源物。在发育过程中,分化的变形虫形成一个由大量孢子组成的子实体,孢子由一个柄支撑。一部分细胞牺牲自己成为非生殖的柄细胞。骗子会破坏多细胞形成的原则,因为骗子细胞改变它们的细胞命运,优先成为孢子。重要的是,盘基网柄菌有基因网络和几种维持多细胞形成的策略。因此,盘基网柄菌可以帮助我们更好地理解参与多细胞形成的保守基因和途径如何也影响癌症的发展,从而可能确定新的治疗途径。

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