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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.

Four Jointed Box 1 Promotes Angiogenesis and Is Associated with Poor Patient Survival in Colorectal Carcinoma