文章：

癌症的信号转导及转录激活因子（STAT）家族蛋白——新的分子靶点成熟

The STATs of cancer —— new molecular targets come of age

原文发布日期：2004-02-01

DOI: 10.1038/nrc1275

类型: Review Article

开放获取: 否

要点：

1. Signal transducer and activator of transcription (STAT)-family proteins are latent cytoplasmic transcription factors that convey signals from cytokine and growth-factor receptors to the nucleus.
2. STAT proteins, particularly STAT3 and the STAT5 proteins, are frequently overactivated in a variety of human solid tumours and blood malignancies.
3. Continuous deregulation of nuclear gene expression by persistent STAT3 and STAT5 signalling promotes the growth and survival of tumour cells, thereby contributing to malignancy.
4. Persistent STAT3 signalling in tumour cells induces tumour angiogenesis and suppresses anti-tumour immune responses, further enhancing tumour progression.
5. Tumour cells that become dependent on persistent STAT3 signalling are more sensitive to STAT3 inhibitors than normal cells, providing a therapeutic window based on transient or partial inhibition of STAT3.
6. Proof-of-concept studies in cell-culture and animal models have validated STAT3 and STAT5 proteins as promising molecular targets for novel cancer therapies, including small-molecule inhibitors of STAT signalling.

要点翻译：

1. 信号转导及转录激活因子（STAT）家族蛋白是潜伏在细胞质中的转录因子，它们将细胞因子和生长因子受体的信号传递至细胞核。
2. STAT蛋白，特别是STAT3和STAT5蛋白，在多种人类实体瘤和血液恶性肿瘤中频繁过度激活。
3. 持续的STAT3和STAT5信号通路通过不断扰乱核内基因表达，促进肿瘤细胞的生长和存活，从而加剧恶性病变。
4. 肿瘤细胞中持续的STAT3信号会诱导肿瘤血管生成并抑制抗肿瘤免疫反应，进一步推动肿瘤进展。
5. 对持续STAT3信号产生依赖的肿瘤细胞相比正常细胞对STAT3抑制剂更为敏感，这为基于短暂或部分抑制STAT3的治疗策略提供了治疗窗口。
6. 在细胞培养和动物模型中开展的概念验证研究已确认STAT3和STAT5蛋白是新型癌症疗法（包括STAT信号通路的小分子抑制剂）极具前景的分子靶点。

英文摘要：

Tumour cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance. STAT proteins — especially STAT3 and STAT5 — regulate all of these processes and are persistently activated in a surprisingly large number of human cancers. Consequently, STAT proteins are emerging — unexpectedly — as ideal targets for cancer therapy.

摘要翻译： 

肿瘤细胞获得失控增殖、抵抗凋亡、维持血管生成以及逃避免疫监视的能力。STAT蛋白——尤其是STAT3和STAT5——调控所有这些过程，并在数量惊人的人类癌症中持续激活。因此，STAT蛋白正出乎意料地成为癌症治疗的理想靶点。

原文链接：

The STATs of cancer — new molecular targets come of age