Cancer cell plasticity: Impact on tumor progression and therapy response
Cancer cell plasticity: Impact on tumor progression and therapy response
复制标题
DOI：
10.1016/j.semcancer.2018.08.009
复制
发表时间：
2018-12-01
影响因子：
14.5
通讯作者：
Munoz, Purification
中科院分区：
文献类型：
--
作者：
da Silva-Diz, Victoria;Lorenzo-Sanz, Laura;Munoz, Purification
大多数肿瘤表现出肿瘤内的异质性，这与疾病进展和对治疗的反应受损有关。癌细胞的可塑性被认为是一种重要的机制，它与遗传和表观遗传改变一起促进了癌细胞的多样性，并促进了肿瘤内的异质性。可塑性赋予癌细胞在分化状态和未分化或癌症干细胞(CSC)状态之间动态转换的能力，分化状态具有有限的致瘤潜力，CSC状态对肿瘤的长期生长负责。此外，它赋予了进入不同的CSC状态的能力，这些CSC具有不同的入侵、传播和种子转移的能力。癌细胞的可塑性与上皮细胞向间充质细胞的转化程序有关，不仅依赖于细胞自主机制，还依赖于肿瘤微环境提供的信号和/或治疗诱导的信号。我们概述了癌细胞状态的动态转变、控制细胞可塑性的机制以及它们对肿瘤进展、转移和治疗反应的影响。了解癌细胞可塑性的机制将为建立新的治疗干预措施提供见解。
Most tumors exhibit intra-tumor heterogeneity, which is associated with disease progression and an impaired response to therapy. Cancer cell plasticity has been proposed as being an important mechanism that, along with genetic and epigenetic alterations, promotes cancer cell diversity and contributes to intra-tumor heterogeneity. Plasticity endows cancer cells with the capacity to shift dynamically between a differentiated state, with limited tumorigenic potential, and an undifferentiated or cancer stem-like cell (CSC) state, which is responsible for longterm tumor growth. In addition, it confers the ability to transit into distinct CSC states with different competence to invade, disseminate and seed metastasis. Cancer cell plasticity has been linked to the epithelial-to-mesenchymal transition program and relies not only on cell-autonomous mechanisms, but also on signals provided by the tumor microenvironment and/or induced in response to therapy. We provide an overview of the dynamic transition for cancer cell states, the mechanisms governing cell plasticity and their impact on tumor progression, metastasis and therapy response. Understanding the mechanisms involved in cancer cell plasticity will provide insights for establishing new therapeutic interventions.