Four Jointed Box One, a Novel Pro-Angiogenic Protein in Colorectal Carcinoma

Abstract

The role of Four jointed box 1 (FJX1) in colorectal cancer (CRC) is presented in this dissertation. FJX1 was identified as a candidate gene for regulating tumor formation in CRC as it was inhibited in rectal cancers after one week treatment with celecoxib. FJX1 mRNA and protein are upregulated in human CRC, and high expression of FJX1 is associated with poor patient prognosis. Novel FJX1 antibodies and expression vectors were developed and used to characterize recombinant FJX1 in vitro. In vivo, FJX1 promotes tumor formation by increasing tumor cell proliferation and vascularization. In vitro, conditioned media from FJX1 expressing cells promoted endothelial cell capillary tube formation in a HIF1-α dependent manner. In addition to these experimental observations, microarray expression profiling of CRC cells with manipulated FJX1 expression is also presented. In sum, these results support the conclusion that FJX1 is a novel regulator of tumor progression, due in part, to its effect on tumor vascularization.