Champalimaud Centre for the Unknown, Lisbon, Portugal.
Department of Surgery, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
Cancer Res. 2022 Dec 16;82(24):4487-4496. doi: 10.1158/0008-5472.CAN-22-2217.
The majority of human cancers evolve over time through the stepwise accumulation of somatic mutations followed by clonal selection akin to Darwinian evolution. However, the in-depth mechanisms that govern clonal dynamics and selection remain elusive, particularly during the earliest stages of tissue transformation. Cell competition (CC), often referred to as 'survival of the fittest' at the cellular level, results in the elimination of less fit cells by their more fit neighbors supporting optimal organism health and function. Alternatively, CC may allow an uncontrolled expansion of super-fit cancer cells to outcompete their less fit neighbors thereby fueling tumorigenesis. Recent research discussed herein highlights the various non-cell-autonomous principles, including interclonal competition and cancer microenvironment competition supporting the ability of a tumor to progress from the initial stages to tissue colonization. In addition, we extend current insights from CC-mediated clonal interactions and selection in normal tissues to better comprehend those factors that contribute to cancer development.
大多数人类癌症是随着时间的推移，通过体细胞突变的逐步积累，然后通过类似于达尔文进化的克隆选择而进化的。然而，控制克隆动态和选择的深入机制仍然难以捉摸，特别是在组织转化的早期阶段。细胞竞争（CC），通常在细胞水平上被称为“适者生存”，导致适应性较差的细胞被适应性更好的邻近细胞消除，从而支持最佳的机体健康和功能。相反，CC 可能会允许超适型癌细胞不受控制地扩张，从而战胜其适应性较差的邻近细胞，从而促进肿瘤发生。本文讨论的最新研究强调了各种非细胞自主原则，包括克隆间竞争和肿瘤微环境竞争，这些原则支持肿瘤从初始阶段发展到组织定植的能力。此外，我们将正常组织中 CC 介导的克隆相互作用和选择的现有见解扩展到更好地理解那些促进癌症发展的因素。
