Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed in many cancer types and in vivo studies have shown that vascular endothelial cell FAK expression and FAK-phosphorylation at tyrosine (Y) 397, and subsequently FAK-Y861, are important in tumour angiogenesis. Pericytes also play a vital role in regulating tumour blood vessel stabilisation, but the specific involvement of pericyte FAK-Y397 and FAK-Y861 phosphorylation in tumour blood vessels is unknown. Using PdgfrβCre + ;FAK^WT/WT, PdgfrβCre + ;FAK^Y397F/Y397F and PdgfrβCre + ;FAK^Y861F/Y861F mice, our data demonstrate that tumour growth, tumour blood vessel density, blood vessel perfusion and pericyte coverage were affected only in late stage tumours in PdgfrβCre + ;FAK^Y861F/Y861F but not PdgfrβCre + ;FAK^Y397F/Y397F mice. Further examination indicates a dual role for pericyte FAK-Y861 phosphorylation in the regulation of tumour vessel regression and also in the control of pericyte derived signals that influence apoptosis in cancer cells. Overall this study identifies the role of pericyte FAK-Y861 in the regulation of tumour vessel regression and tumour growth control and that non-phosphorylatable FAK-Y861F in pericytes reduces tumour growth and blood vessel density.

粘着斑激酶 (FAK) 是一种非受体酪氨酸激酶，在许多癌症类型中过度表达，体内研究表明，血管内皮细胞 FAK 表达和酪氨酸 (Y) 397 以及随后的 FAK-Y861 处的 FAK 磷酸化与血管内皮细胞的 FAK 磷酸化有关。在肿瘤血管生成中发挥重要作用。周细胞在调节肿瘤血管稳定方面也发挥着至关重要的作用，但周细胞FAK-Y397和FAK-Y861磷酸化在肿瘤血管中的具体参与尚不清楚。使用PdgfrβCre + ； FAK ^WT/WT , PdgfrβCre + ; FAK ^Y397F/Y397F和PdgfrβCre + ； FAK ^Y861F/Y861F小鼠，我们的数据表明PdgfrβCre + 中的肿瘤生长、肿瘤血管密度、血管灌注和周细胞覆盖仅在晚期肿瘤中受到影响； FAK ^Y861F/Y861F但不是PdgfrβCre + ； FAK ^Y397F/Y397F小鼠。进一步的检查表明，周细胞 FAK-Y861 磷酸化在调节肿瘤血管消退以及控制影响癌细胞凋亡的周细胞衍生信号方面具有双重作用。总体而言，这项研究确定了周细胞 FAK-Y861 在调节肿瘤血管消退和肿瘤生长控制中的作用，并且周细胞中的非磷酸化 FAK-Y861F 可降低肿瘤生长和血管密度。