Adhesion and Angiogenesis Laboratory, Centre for Tumour Biology, Barts Cancer Institute, a CR-UK Centre of Excellence, Queen Mary University of London, UK.
J Pathol. 2012 Jan;226(2):404-12. doi: 10.1002/path.3018. Epub 2011 Nov 23.
Angiogenesis, the formation of new blood vessels from pre-existing ones, is essential for tumour development. It is initiated and regulated by growth factors via their surface receptors, which activate several intracellular signalling pathways in endothelial cells. Cell adhesion molecules, such as integrins, also regulate angiogenesis. Despite these facts, inhibitors of endothelial cell growth factor receptors or integrins have not been as effective as initially hoped in the long-term inhibition of angiogenesis in cancer patients. Signalling downstream of growth factor receptors and integrins converge on the ubiquitously expressed non-receptor tyrosine kinase focal adhesion kinase (FAK). FAK is involved in endothelial cell proliferation, migration and survival, is up-regulated in many cancers and has recently been shown to control tumour angiogenesis. Indeed, FAK inhibitors are presently being developed for the treatment of cancer. However, recent studies have indicated the complexities of understanding the precise role for FAK in angiogenesis. Here we have summarized some of the key features of FAK, addressed some of the apparently contradictory roles of this molecule in angiogenesis and provided some perspectives for future studies.
血管生成，即从预先存在的血管中形成新的血管，对于肿瘤的发展至关重要。它是由生长因子通过其表面受体启动和调节的，这些受体激活内皮细胞中的几个细胞内信号通路。细胞黏附分子，如整合素，也调节血管生成。尽管有这些事实，但内皮细胞生长因子受体或整合素的抑制剂在长期抑制癌症患者的血管生成方面并没有最初预期的那么有效。生长因子受体和整合素下游的信号转导集中在普遍表达的非受体酪氨酸激酶粘着斑激酶（FAK）上。FAK 参与内皮细胞的增殖、迁移和存活，在许多癌症中上调，并最近被证明可以控制肿瘤血管生成。事实上，目前正在开发 FAK 抑制剂用于癌症治疗。然而，最近的研究表明，要了解 FAK 在血管生成中的精确作用非常复杂。在这里，我们总结了 FAK 的一些关键特征，解决了该分子在血管生成中一些明显矛盾的作用，并为未来的研究提供了一些观点。
