文章：

播散性癌细胞休眠机制：一个觉醒的领域

Mechanisms of disseminated cancer cell dormancy: an awakening field

原文发布日期：2014-08-14

DOI: 10.1038/nrc3793

类型: Review Article

开放获取: 否

要点：

1. It is thought that dormant disseminated tumour cells (DTCs) are the cellular entity responsible for clinical dormancy and subsequent metastasis after surgery and adjuvant treatment.
2. Cellular dormancy is regulated by intrinsic and autocrine signals, as well as signals derived from immune and endothelial cells. Stress signalling pathways activated by exogenous stressors, intrinsic damage or microenvironmental cues can trigger dormancy.
3. The balance between ERK and p38 signalling regulates dormancy versus proliferation decisions in different cancer models.
4. Autophagy is important for the induction of dormancy and cell survival. Morphogenetic cues and intrinsic pathways that regulate cell quiescence and pluripotency or 'stemness' might also coordinate DTC dormancy.
5. Mechanisms that were thought to regulate tumour mass dormancy, such as cytotoxic CD8⁺ T cells or non-angiogenic endothelial cells, may in fact regulate cellular dormancy.
6. Pathways and mechanisms regulating cellular dormancy can be manipulated to induce dormancy.
7. Dormancy models have identified gene signatures that are predictive of delayed onset of metastasis in patients and have provided a first shortlist of genes that may serve as dormancy markers to test in DTCs.

要点翻译：

1. 据认为，休眠的播散性肿瘤细胞（DTCs）是导致临床休眠及术后辅助治疗后发生后续转移的细胞实体。
2. 细胞休眠受内在信号、自分泌信号以及源自免疫细胞和内皮细胞的信号共同调控。外源性应激源、内在损伤或微环境信号激活的应激信号通路可触发休眠状态。
3. 在不同癌症模型中，ERK与p38信号通路之间的平衡调控着休眠与增殖的抉择。
4. 自噬对诱导休眠和维持细胞存活至关重要。调节细胞静息与多能性（或称“干性”）的形态发生信号和内在通路也可能协调DTCs的休眠。
5. 曾被认为调控肿瘤团块休眠的机制（如细胞毒性CD8+ T细胞或非血管生成性内皮细胞）实际上可能调控细胞休眠。
6. 调控细胞休眠的通路和机制可被用于诱导休眠状态。
7. 休眠模型已鉴定出可预测患者转移延迟发生的基因特征，并提供了首批可作为DTCs休眠标记物进行测试的候选基因清单。

英文摘要：

Metastases arise from residual disseminated tumour cells (DTCs). This can happen years after primary tumour treatment because residual tumour cells can enter dormancy and evade therapies. As the biology of minimal residual disease seems to diverge from that of proliferative lesions, understanding the underpinnings of this new cancer biology is key to prevent metastasis. Analysis of approximately 7 years of literature reveals a growing focus on tumour and normal stem cell quiescence, extracellular and stromal microenvironments, autophagy and epigenetics as mechanisms that dictate tumour cell dormancy. In this Review, we attempt to integrate this information and highlight both the weaknesses and the strengths in the field to provide a framework to understand and target this crucial step in cancer progression.

摘要翻译： 

转移瘤源于残留的播散性肿瘤细胞（DTCs）。由于这些残留细胞可进入休眠状态并逃避治疗，这种现象可能在原发瘤治疗多年后发生。微小残留病灶的生物学特征与增殖性病变显著不同，揭示这一新型癌症生物学机制是预防转移的关键。对近7年文献的分析显示，研究日益聚焦于肿瘤及正常干细胞的静息状态、细胞外与基质微环境、自噬及表观遗传学等调控肿瘤细胞休眠的机制。本综述整合现有信息，指出该领域的优势与不足，旨在为理解并靶向癌症进展这一关键步骤提供理论框架。

原文链接：

Mechanisms of disseminated cancer cell dormancy: an awakening field