Institute for Computational Medicine, NYU Langone Health, New York, New York 10016, USA.
Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, New York 10016, USA.
Genome Res. 2021 Oct;31(10):1719-1727. doi: 10.1101/gr.275308.121.
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.
肿瘤恶性细胞内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研究工作已经确定了多种癌症类型中不同的癌症细胞状态，但它们的功能相关性以及它们为肿瘤系统提供的优势仍然难以捉摸。我们在这里根据一致和差异表达的基因模块来定义癌症细胞状态，并回顾状态对整个肿瘤系统的起源、动态和影响。恶性细胞群体所呈现的细胞状态范围可能取决于细胞谱系、表观遗传历史、基因突变或环境线索，这对单个状态的相对稳定性或可塑性有影响。最后，有证据表明，肿瘤微环境中的不同状态的恶性细胞可能相互合作或竞争，从而通过增加免疫逃逸、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癌症细胞状态起源和动态的机制可能有助于了解异质性如何促进肿瘤适应性，并突出可用于治疗的脆弱性。
