文章：

TIMPs：癌症中多功能细胞外调节因子

TIMPs: versatile extracellular regulators in cancer

原文发布日期：2016-12-09

DOI: 10.1038/nrc.2016.115

类型: Review Article

开放获取: 否

要点：

1. Tissue inhibitors of metalloproteinases (TIMPs) control diverse metalloproteinases and their wide range of substrates, regulating tissue homeostasis.
2. TIMPs are tightly involved in the development of most cancer hallmarks.
3. TIMP-regulated proteolytic processing affects major signalling pathways.
4. TIMP genetic models suggest TIMPs have a role in adult stem cell niches.
5. TIMP1 and TIMP3 have contrasting correlations with prognosis in human cancers: TIMP1 increase and TIMP3 reduction indicate poor prognosis.
6. TIMPs have the potential to function as biomarkers in patient body fluids.

要点翻译：

1. 金属蛋白酶组织抑制剂（TIMPs）通过调控多样的金属蛋白酶及其广泛底物，维持组织稳态。
2. TIMPs深度参与大多数癌症特征的发展过程。
3. TIMP调控的蛋白水解过程影响主要信号通路。
4. TIMP基因模型表明TIMPs在成体干细胞微环境中发挥作用。
5. TIMP1和TIMP3在人类癌症中与预后呈现相反相关性：TIMP1升高与TIMP3降低均提示不良预后。
6. TIMPs具备作为患者体液中生物标志物的潜力。

英文摘要：

A compelling long-term goal of cancer biology is to understand the crucial players during tumorigenesis in order to develop new interventions. Here, we review how the four non-redundant tissue inhibitors of metalloproteinases (TIMPs) regulate the pericellular proteolysis of a vast range of matrix and cell surface proteins, generating simultaneous effects on tumour architecture and cell signalling. Experimental studies demonstrate the contribution of TIMPs to the majority of cancer hallmarks, and human cancers invariably show TIMP deregulation in the tumour or stroma. Of the four TIMPs, TIMP1 overexpression or TIMP3 silencing is consistently associated with cancer progression or poor patient prognosis. Future efforts will align mouse model systems with changes in TIMPs in patients, will delineate protease-independent TIMP function, will pinpoint therapeutic targets within the TIMP–metalloproteinase–substrate network and will use TIMPs in liquid biopsy samples as biomarkers for cancer prognosis.

摘要翻译： 

癌症生物学的一个引人注目的长期目标是理解肿瘤发生过程中的关键参与者，以便开发新的干预措施。在此，我们回顾了四种非冗余的组织金属蛋白酶抑制剂（TIMPs）如何调控大量基质和细胞表面蛋白的周围蛋白水解，同时对肿瘤结构和细胞信号传导产生同步影响。实验研究表明，TIMPs对大多数癌症特征具有贡献，人类癌症在肿瘤或基质中普遍存在TIMPs的失调。在四种TIMPs中，TIMP1的过表达或TIMP3的沉默始终与癌症进展或患者预后不良相关。未来的努力将把小鼠模型系统与患者TIMPs的变化相结合，阐明不依赖蛋白酶的TIMP功能，确定TIMP-金属蛋白酶-底物网络中的治疗靶点，并将TIMPs用于液体活检样本中作为癌症预后的生物标志物。

原文链接：

TIMPs: versatile extracellular regulators in cancer