本期Nature Communications上发表的一项研究表明，通过抑制蛋白“粘着斑激酶”(FAK) 来治疗癌症可能并不像以前所认为的那样简单。以高剂量使用的FAK抑制因子已被发现对控制癌症有显着效果。然而，这项研究却显示，FAK在癌症病情发展中所起的生物学作用是复杂的，这种酶的部分抑制可能会增强、而不是降低肿瘤生长。
FAK表达在身体的大多数细胞中，调控一系列生理过程，其中包括新血管的形成（一个被称为“血管生成”的过程）。因为肿瘤依靠血管生成来保证它们持续生长所需的养分供应，所以FAK抑制因子目前正在作为抗癌药物被开发。Vassiliki Kostourou及其同事通过基因工程方法培育出产生低水平FAK的小鼠，发现矛盾的是，这些小鼠身上的肿瘤比正常小鼠长得更大、有更多新的血管。同样情况也出现在用低剂量的一种FAK抑制因子处理过的正常小鼠身上。这与以下假设形成鲜明对比：FAK抑制一般会减慢肿瘤生长；该假设促使人们将FAK抑制因子作为抗癌药物开发。
这些发现表明，高剂量的FAK抑制因子（它们确保这种酶被完全抑制）也许是实现治疗成功所必需的。（生物谷Bioon.com）
生物谷推荐英文摘要：
Nature Communications DOI:10.1038/ncomms3020
FAK-heterozygous mice display enhanced tumour angiogenesis
Vassiliki Kostourou, Tanguy Lechertier, Louise E. Reynolds, Delphine M. Lees, Marianne Baker, Dylan T. Jones, Bernardo Tavora, Antoine R. Ramjaun, Graeme M. Birdsey, Stephen D. Robinson, Maddy Parsons, Anna M. Randi, Ian R. Hart & Kairbaan Hodivala-Dilke
Genetic ablation of endothelial focal adhesion kinase (FAK) can inhibit pathological angiogenesis, suggesting that loss of endothelial FAK is sufficient to reduce neovascularization. Here we show that reduced stromal FAK expression in FAK-heterozygous mice unexpectedly enhances both B16F0 and CMT19T tumour growth and angiogenesis. We further demonstrate that cell proliferation and microvessel sprouting, but not migration, are increased in serum-stimulated FAK-heterozygous endothelial cells. FAK-heterozygous endothelial cells display an imbalance in FAK phosphorylation at pY397 and pY861 without changes in Pyk2 or Erk1/2 activity. By contrast, serum-stimulated phosphorylation of Akt is enhanced in FAK-heterozygous endothelial cells and these cells are more sensitive to Akt inhibition. Additionally, low doses of a pharmacological FAK inhibitor, although too low to affect FAK autophosphorylation in vitro, can enhance angiogenesis ex vivo and tumour growth in vivo. Our results highlight a potential novel role for FAK as a nonlinear, dose-dependent regulator of angiogenesis where heterozygous levels of FAK enhance angiogenesis.
