FOXC2转录因子促进肿瘤血管生成的研究进展

Research progress of FOXC2 transcription factor in tumor angiogenesis

近年来,以血管内皮生长因子(vascular endothelial growth factor,VEGF)为靶点限制肿瘤生长和疾病进展的治疗方法已经应用于临床。但是,调节病理性血管生成的机制尚不十分清楚。FOXC2(forkheadbox C2)在肿瘤血管形成中发挥重要作用。在FOXC2突变小鼠(FOXC2+/-)黑素瘤中,肿瘤生长速度减缓,新生血管数量减少,这与肿瘤血管周细胞(mural-cell)覆盖减少和肿瘤血管内皮细胞凋亡增加有关。而且,FOXC2也能促进肿瘤细胞的上皮间质转化(epithelial-mesenchymal transition,EMT),说明FOXC2是促进肿瘤血管生成和肿瘤细胞浸润和转移的重要因子,极有可能成为抗肿瘤血管生成治疗的靶点。

Recent years, therapies that target vascular endothelial growth factor （VEGF） to limit tumor angiogenesis and subsequent disease progression have been approved. However, mechanisms of regulatory pathological angiogenesis remain unknown. FOXC2 （forkhead box C2） is critical for tumor vascular formation. Recent studies have shown that FOXC2 deficiency reduced tumor growth and vascularization in a B16 mouse melanoma model, which was associated with decrease in mural-cell coverage and increase in endothelial-cell apoptosis in tumor blood vessels. Besides, FOXC2 can also promote epithelial-mesenchymal transition （EMT） in several types of tumors such as breast, colon tumors. Collectively, these findings suggest that FOXC2 is essential for tumor angiogenesis and may be a target for cancer therapy.