文章：

病灶黏附激酶在癌症中的作用-一个新的治疗机会

The role of focal-adhesion kinase in cancer — a new therapeutic opportunity

原文发布日期：2005-07-01

DOI: 10.1038/nrc1647

类型: Review Article

开放获取: 否

要点：

1. Focal-adhesion kinase (FAK) is a non-receptor tyrosine kinase that provides signalling and scaffolding functions at sites of integrin adhesion. It is involved in the regulation of turnover of these adhesion sites, a process that is crucial in the control of cell migration.
2. FAK is linked to the protection of cells from anoikis (suspension-induced cell death). This anti-apoptotic function is potentially linked to the ability of FAK to sequester receptor-interacting protein (RIP) from the death-receptor machinery.
3. Substantial circumstantial evidence has accumulated linking overexpression of FAK to a wide range of human epithelial cancers. Levels of FAK expression correlate with the invasive potential of tumours.
4. Using a mouse model of skin carcinogenesis, a direct requirement for FAK has now been shown during tumour progression in vivo. These observations are probably linked to the ability of FAK to protect cells from apoptosis.
5. Inhibition of FAK function might provide an attractive anticancer target, however it is not yet clear what the most effective strategy would be. Potential intervention routes are inhibition of the kinase activity of FAK or disruption of crucial protein–protein interactions.

要点翻译：

1. 黏着斑激酶（FAK）是一种非受体酪氨酸激酶，在整合素黏附位点发挥信号传导和支架功能。它参与调控这些黏附位点的更新过程，该过程对细胞迁移的控制至关重要。
2. FAK与保护细胞免受失巢凋亡（悬浮诱导的细胞死亡）有关。这种抗凋亡功能可能与FAK从死亡受体机制中隔离受体相互作用蛋白（RIP）的能力相关。
3. 大量间接证据表明，FAK的过度表达与多种人类上皮性癌症相关。FAK的表达水平与肿瘤的侵袭潜力呈正相关。
4. 通过皮肤癌发生的小鼠模型研究，现已证实FAK在体内肿瘤进展过程中具有直接必要性。这些观察结果很可能与FAK保护细胞免于凋亡的能力有关。
5. 抑制FAK功能可能成为一个有吸引力的抗癌靶点，但目前尚不清楚最有效的策略是什么。潜在的干预途径包括抑制FAK的激酶活性或破坏关键的蛋白质-蛋白质相互作用。

英文摘要：

Focal-adhesion kinase (FAK) is an important mediator of growth-factor signalling, cell proliferation, cell survival and cell migration. Given that the development of malignancy is often associated with perturbations in these processes, it is not surprising that FAK activity is altered in cancer cells. Mouse models have shown that FAK is involved in tumour formation and progression, and other studies showing that FAK expression is increased in human tumours make FAK a potentially important new therapeutic target.

摘要翻译： 

黏着斑激酶（FAK）是生长因子信号传导、细胞增殖、细胞存活和细胞迁移的重要介质。鉴于恶性肿瘤的发生常伴随这些过程的紊乱，FAK活性在癌细胞中发生改变并不令人惊讶。小鼠模型已显示FAK参与肿瘤的形成与进展，而其他研究表明FAK在人肿瘤中的表达增加，使FAK成为潜在的重要新治疗靶点。

原文链接：

The role of focal-adhesion kinase in cancer — a new therapeutic opportunity