Nagata Rina, Igaki Tatsushi
Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Dev Growth Differ. 2018 Dec;60(9):522-530. doi: 10.1111/dgd.12575. Epub 2018 Nov 15.
Cell competition is a context-dependent cell elimination through short-range cell-cell interaction, in which cells with higher fitness eliminate neighboring less-fit or oncogenic cells within the growing tissue. Cell competition can be triggered by many different factors such as heterozygous mutations in the ribosomal protein genes (which are called "Minute" mutations), elevated Myc, Yorkie/YAP, Wg/Wnt, JAK-STAT, Ras, or Src activity, and loss of Mahjong/VprBP, endocytic pathway components, or apicobasal cell polarity. Studies on the mechanisms and roles of cell competition have suggested that cell competition can be divided into two types: selection of fitter cells or elimination of oncogenic cells. The former type of cell competition includes Minute or Myc-induced cell competition that is considered to be dependent on the relative level of protein synthesis. The later type of cell competition includes tumor-suppressive cell competition triggered by loss of cell polarity genes such as scribble (scrib) or discs large (dlg). Genetic studies in Drosophila during the past decade have provided significant progress in understanding the mechanisms of these phenomena. At the same time, these studies have now raised new questions; how do different mechanisms contribute or cooperate to drive cell competition, do common mechanisms exist in different types of cell competition, and what are the physiological roles of these cell competition phenomena?
细胞竞争是一种通过短程细胞-细胞相互作用实现的、依赖于环境的细胞消除过程,在此过程中,适应性更强的细胞会消除生长组织内相邻的适应性较差或致癌的细胞。细胞竞争可由多种不同因素触发,如核糖体蛋白基因中的杂合突变(称为“Minute”突变)、Myc、Yorkie/YAP、Wg/Wnt、JAK-STAT、Ras或Src活性升高,以及Mahjong/VprBP、内吞途径成分或顶-基细胞极性的丧失。对细胞竞争机制和作用的研究表明,细胞竞争可分为两种类型:选择适应性更强的细胞或消除致癌细胞。前一种类型的细胞竞争包括Minute或Myc诱导的细胞竞争,这种竞争被认为依赖于蛋白质合成的相对水平。后一种类型的细胞竞争包括由细胞极性基因(如scribble,简称scrib或 discs large,简称dlg)缺失引发的肿瘤抑制性细胞竞争。过去十年中在果蝇中的遗传学研究在理解这些现象的机制方面取得了重大进展。与此同时,这些研究现在也提出了新的问题:不同的机制如何促成或协同驱动细胞竞争,不同类型的细胞竞争中是否存在共同机制,以及这些细胞竞争现象的生理作用是什么?