Cancer cell states and emergent properties of the dynamic tumor system.
Cancer cell states and emergent properties of the dynamic tumor system.
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DOI：
10.1101/gr.275308.121
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发表时间：
2021-10
期刊：
影响因子：
7
通讯作者：
Yanai I
中科院分区：
文献类型：
--
作者：
Barkley D;Rao A;Pour M;França GS;Yanai I
肿瘤恶性细胞的表型异质性正在成为肿瘤发生的一个关键特性。最近使用单细胞转录组学的工作已经导致在一系列癌症类型中识别出不同的癌细胞状态，但是它们的功能相关性和它们作为一个系统为肿瘤提供的优势仍然难以捉摸。在这里，我们提出了癌细胞状态的定义，从连贯和差异表达的基因模块和回顾的起源，动态和状态对肿瘤系统的影响作为一个整体。恶性群体的细胞状态谱可能取决于细胞谱系、表观遗传史、基因突变或环境因素，这对个体状态的相对稳定性或可塑性有影响。最后，有证据表明，不同状态的恶性细胞可能在肿瘤生态位内合作或竞争，从而通过增加免疫逃避、耐药性或侵袭性为肿瘤提供进化优势。揭示肿瘤发生过程中控制癌细胞状态起源和动态的机制可能会揭示异质性如何促进肿瘤适应性，并突出可用于治疗的脆弱性。
Phenotypic heterogeneity within malignant cells of a tumor is emerging as a key property of tumorigenesis. Recent work using single-cell transcriptomics has led to the identification of distinct cancer cell states across a range of cancer types, but their functional relevance and the advantage that they provide to the tumor as a system remain elusive. We present here a definition of cancer cell states in terms of coherently and differentially expressed gene modules and review the origins, dynamics, and impact of states on the tumor system as a whole. The spectrum of cell states taken on by a malignant population may depend on cellular lineage, epigenetic history, genetic mutations, or environmental cues, which has implications for the relative stability or plasticity of individual states. Finally, evidence has emerged that malignant cells in different states may cooperate or compete within a tumor niche, thereby providing an evolutionary advantage to the tumor through increased immune evasion, drug resistance, or invasiveness. Uncovering the mechanisms that govern the origin and dynamics of cancer cell states in tumorigenesis may shed light on how heterogeneity contributes to tumor fitness and highlight vulnerabilities that can be exploited for therapy.