Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, United States of America.
PLoS One. 2013 Jul 29;8(7):e69660. doi: 10.1371/journal.pone.0069660. Print 2013.
Angiogenesis, the recruitment and re-configuration of pre-existing vasculature, is essential for tumor growth and metastasis. Increased tumor vascularization often correlates with poor patient outcomes in a broad spectrum of carcinomas. We identified four jointed box 1 (FJX1) as a candidate regulator of tumor angiogenesis in colorectal cancer. FJX1 mRNA and protein are upregulated in human colorectal tumor epithelium as compared with normal epithelium and colorectal adenomas, and high expression of FJX1 is associated with poor patient prognosis. FJX1 mRNA expression in colorectal cancer tissues is significantly correlated with changes in known angiogenesis genes. Augmented expression of FJX1 in colon cancer cells promotes growth of xenografts in athymic mice and is associated with increased tumor cell proliferation and vascularization. Furthermore, FJX1 null mice develop significantly fewer colonic polyps than wild-type littermates after combined dextran sodium sulfate (DSS) and azoxymethane (AOM) treatment. In vitro, conditioned media from FJX1 expressing cells promoted endothelial cell capillary tube formation in a HIF1-α dependent manner. Taken together our results support the conclusion that FJX1 is a novel regulator of tumor progression, due in part, to its effect on tumor vascularization.
血管生成，即预先存在的脉管系统的募集和重新配置，对肿瘤的生长和转移至关重要。在广泛的癌种中，肿瘤血管生成的增加通常与患者预后不良相关。我们发现四个联合盒 1（FJX1）是结直肠癌肿瘤血管生成的候选调节剂。与正常上皮组织和结直肠腺瘤相比，人结直肠肿瘤上皮中的 FJX1 mRNA 和蛋白表达上调，并且 FJX1 高表达与患者预后不良相关。结直肠癌组织中 FJX1 mRNA 的表达与已知的血管生成基因的变化显著相关。在结肠癌细胞中增强 FJX1 的表达可促进裸鼠异种移植物的生长，并与肿瘤细胞增殖和血管生成增加相关。此外，联合给予葡聚糖硫酸钠（DSS）和氧化偶氮甲烷（AOM）后，FJX1 缺失小鼠比野生型同窝小鼠形成的结肠息肉明显减少。在体外，表达 FJX1 的细胞的条件培养基以依赖 HIF1-α的方式促进内皮细胞毛细血管管形成。综上所述，我们的研究结果支持 FJX1 是肿瘤进展的新型调节剂的结论，部分原因是其对肿瘤血管生成的影响。
