文章：

Notch在肿瘤发生中的作用：致癌基因还是肿瘤抑制因子？

The role of Notch in tumorigenesis: oncogene or tumour suppressor?

原文发布日期：2003-12-01

DOI: 10.1038/nrc1186

类型: Review Article

开放获取: 否

要点：

1. Signalling between Notch receptors and ligands influences many differentiation processes and cell-fate decisions during embryonic and postnatal development.
2. Stem-cell maintenance, binary cell-fate decisions and induction of differentiation are three main functions of Notch signalling in self-renewing tissues.
3. Notch can function as an oncogene. Aberrant expression of the dominant active cytoplasmic domain of Notch receptors in haematopoietic cells because of chromosomal translocation or viral integrations causes T-cell leukaemias in mice and humans.
4. Notch needs to cooperate with oncoproteins that can override the G1–S checkpoint in order to cause cancer.
5. Notch receptors and ligands are re-expressed in certain human carcinomas, which is compatible with the ability of Notch to maintain stem cells or precursor cells in an undifferentiated state.
6. Recent data show that Notch1 can also function as a tumour suppressor in mouse skin by inducing Waf1 and repressing Shh and Wnt signalling.
7. Notch has two faces; one that promotes and the other that suppresses tumorigenesis. Which of the two faces is shown is dependent on the cellular context and the crosstalk with other signal-transduction pathways.

要点翻译：

1. Notch受体与配体间的信号传导影响胚胎及出生后发育过程中的诸多分化进程与细胞命运决定。
2. 在自我更新组织中，Notch信号主要发挥三大功能：维持干细胞特性、调控二元细胞命运抉择以及诱导分化。
3. Notch可作为原癌基因发挥作用。由于染色体易位或病毒整合导致造血细胞中Notch受体显性活性胞质结构域的异常表达，会引发小鼠和人类的T细胞白血病。
4. Notch需与能够突破G1-S期检查点的癌蛋白协同作用才能诱发癌症。
5. Notch受体和配体在特定人类癌组织中重新表达，这与Notch维持干细胞或前体细胞处于未分化状态的能力相吻合。
6. 最新研究表明，Notch1通过诱导Waf1及抑制Shh和Wnt信号通路，在小鼠皮肤中亦可发挥肿瘤抑制因子作用。
7. Notch具有双重面孔：一方面促进肿瘤发生，另一方面抑制肿瘤发生。具体呈现哪种特性取决于细胞微环境以及与其他信号转导通路的交互作用。

英文摘要：

Notch signalling participates in the development of multicellular organisms by maintaining the self-renewal potential of some tissues and inducing the differentiation of others. Involvement of Notch in cancer was first highlighted in human T-cell leukaemia, fuelling the notion that aberrant Notch signalling promotes tumorigenesis. However, there is mounting evidence that Notch signalling is not exclusively oncogenic. It can instead function as a tumour suppressor.

摘要翻译： 

Notch信号通过维持某些组织的自我更新潜力并诱导其他组织的分化，参与多细胞生物的发育。Notch在癌症中的作用最初是在人类T细胞白血病中被强调的，这助长了异常Notch信号促进肿瘤发生的观点。然而，越来越多的证据表明，Notch信号并非完全是致癌的，它也可以作为肿瘤抑制因子发挥作用。

原文链接：

The role of Notch in tumorigenesis: oncogene or tumour suppressor?