文章：

NF-κB亚基在癌症中的复杂多样作用

The diverse and complex roles of NF-κB subunits in cancer

原文发布日期：2012-01-19

DOI: 10.1038/nrc3204

类型: Review Article

开放获取: 否

要点：

1. The nuclear factor-κB (NF-κB)–inhibitor of NF-κB kinase (IKK) pathway can promote the growth and survival of many solid and haematological maligancies and therefore has the potential to provide numerous targets for novel anticancer therapies.
2. Most attention has focused on the development of IKKβ inhibitors, but it is now clear that IKKβ has many NF-κB-independent functions and its inhibition could result in undesired effects.
3. Although it is apparent that NF-κB subunits have important roles in tumorigenesis and the response to cancer therapy, their individual contributions have not been clearly defined.
4. The NF-κB response is highly pleiotropic and the consequences of its activation can be context dependent. NF-κB is not always tumour promoting and it can exhibit tumour suppressor-like activities.
5. Crosstalk with tumour-suppressor proteins, such as p53, provides an important mechanism for regulating NF-κB activity and function in cancer. Tumour suppressors can inhibit the tumour-promoting activities of NF-κB subunits while facilitating their ability to suppress cancer progression.
6. Understanding the regulation and function of the NF-κB subunits in cancer provides opportunities for the development of new therapies and allows the better use of existing drugs that affect NF-κB–IKK activity.

要点翻译：

1. 核因子κB（NF-κB）–IKK激酶通路能促进多种实体瘤和血液恶性肿瘤的生长与存活，因此有望为新型抗癌疗法提供多个靶点。
2. 目前研究主要聚焦于IKKβ抑制剂的开发，但现已明确IKKβ具有诸多不依赖NF-κB的功能，其抑制可能引发不良效应。
3. 虽然NF-κB亚基在肿瘤发生和癌症治疗应答中具有重要作用已是不争事实，但各亚基的具体功能尚未明确。
4. NF-κB应答具有高度多效性，其激活后果可能因具体情境而异。NF-κB并非始终促进肿瘤，它也能表现出类肿瘤抑制活性。
5. 与p53等肿瘤抑制蛋白的交互作用，为调控NF-κB在癌症中的活性与功能提供了重要机制。肿瘤抑制蛋白可抑制NF-κB亚基的促瘤活性，同时增强其抑制癌症进展的能力。
6. 理解NF-κB亚基在癌症中的调控机制与功能，不仅为开发新疗法创造机遇，也有助于更有效地运用现有影响NF-κB–IKK活性的药物。

英文摘要：

It is only recently that the full importance of nuclear factor-κB (NF-κB) signalling to cancer development has been understood. Although much attention has focused on the upstream pathways leading to NF-κB activation, it is now becoming clear that the inhibitor of NF-κB kinases (IKKs), which regulate NF-κB activation, have many independent functions in tissue homeostasis and normal immune function that could compromise the clinical utility of IKK inhibitors. Therefore, if the NF-κB pathway is to be properly exploited as a target for both anticancer and anti-inflammatory drugs, it is appropriate to reconsider the complex roles of the individual NF-κB subunits.

摘要翻译： 

直到最近，人们才完全认识到核因子-κB（NF-κB）信号通路在癌症发生中的重要作用。尽管大量研究聚焦于激活NF-κB的上游通路，但现在越来越明确的是，调控NF-κB激活的NF-κB抑制因子激酶（IKKs）在组织稳态和正常免疫功能中具有许多独立功能，这可能会限制IKK抑制剂的临床应用价值。因此，如果要将NF-κB通路作为抗癌和抗炎药物的靶点进行有效利用，就有必要重新评估各个NF-κB亚基所发挥的复杂作用。

原文链接：

The diverse and complex roles of NF-κB subunits in cancer