文章：

转移抑制因子改变癌细胞的信号转导

Metastasis suppressors alter the signal transduction of cancer cells

原文发布日期：2003-01-01

DOI: 10.1038/nrc967

类型: Review Article

开放获取: 否

要点：

1. Metastasis-suppressor genes are identified by their reduced expression in highly metastatic, compared with tumorigenic but poorly or non-metastatic, tumour cells. Following re-expression of a metastasis-suppressor gene in a tumour cell line, in vivo metastasis is inhibited, without a significant reduction in tumorigenicity.
2. Eight metastasis-suppressor genes have been confirmed so far. They affect many aspects of signal transduction, including pathways that are involved in invasion, growth-factor-receptor signalling, the mitogen-activated protein kinase pathway, cell–cell communication and transcription.
3. Many metastasis suppressors affect metastatic colonization — the final outgrowth of tumour cells after they have arrived at a distant site — by non-angiogenic means. Re-expression of metastasis-suppressor expression in micrometastatic tumour cells might halt their further progression with a clinical benefit.
4. The loss of metastasis-suppressor expression in metastatic lesions indicates that several aspects of signal transduction are compromised, compared with non-metastatic tumour cells. Preclinical drug testing based on primary tumour size in mice might not reflect these important differences, and metastatically competent model systems might predict clinical efficacy more accurately.

要点翻译：

1. 转移抑制基因的鉴定依据是：与具有成瘤性但低转移或无转移能力的肿瘤细胞相比，在高转移性肿瘤细胞中这些基因的表达水平降低。在肿瘤细胞系中重新表达转移抑制基因后，体内转移过程受到抑制，但肿瘤形成能力并未显著减弱。
2. 目前已有八种转移抑制基因被确认。这些基因影响信号转导的多个方面，包括参与侵袭、生长因子受体信号传导、丝裂原活化蛋白激酶通路、细胞间通讯及转录过程的信号途径。
3. 许多转移抑制因子通过非血管生成方式影响转移定植——即肿瘤细胞抵达远端部位后的最终外扩生长过程。在微转移性肿瘤细胞中重新表达转移抑制基因，可能阻止其进一步进展并带来临床获益。
4. 转移性病灶中转移抑制基因表达的缺失表明，与非转移性肿瘤细胞相比，其信号转导的多个环节存在功能障碍。基于小鼠原发肿瘤大小的临床前药物试验可能无法反映这些关键差异，而具备转移能力的模型系统或许能更准确地预测临床疗效。

英文摘要：

Tumour metastasis is a significant contributor to death in cancer patients. Eight metastasis-suppressor genes that reduce the metastatic propensity of a cancer cell line in vivo without affecting its tumorigenicity have been identified. These affect important signal-transduction pathways, including mitogen-activated protein kinases, RHO, RAC and G-protein-coupled and tyrosine-kinase receptors. So how might we use this knowledge to improve the treatment of patients with cancer?

摘要翻译： 

肿瘤转移是癌症患者死亡的重要原因。目前已发现8个转移抑制基因，它们能在体内降低癌细胞系的转移倾向，而不影响其致瘤性。这些基因作用于重要的信号转导通路，包括丝裂原活化蛋白激酶、RHO、RAC以及G蛋白偶联受体和酪氨酸激酶受体。那么，我们如何利用这些知识来改善癌症患者的治疗呢？

原文链接：

Metastasis suppressors alter the signal transduction of cancer cells