Abstract
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.
Highlights
Angiogenesis is the process of recruiting and restructuring blood vessels from pre-existing vasculature
Lee Moffitt Cancer Center (MCC) revealed that four jointed box 1 (FJX1) mRNA is significantly increased across all stages of CRC as compared to normal colorectal tissue and colorectal adenomas (Figure 1A, stage 1, P,0.02; stages 2, 3 and 4, P,0.00001)
We identified FJX1 as a candidate target of cyclooxygenase 2 (COX-2) activity associated with poor outcomes in CRC
Summary
Angiogenesis is the process of recruiting and restructuring blood vessels from pre-existing vasculature. Metastatic disease is reliant on vascular routes, and increased tumor angiogenesis often correlates with poor patient outcomes in a variety of carcinomas. Secreted angiogenic factors, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), ephrins, netrins, and slits, are often overexpressed in cancer and provide cues that affect endothelial cell proliferation, migration, and invasion. Elevated expression of COX-2 has been detected in colorectal carcinoma (CRC) compared to normal mucosa and correlated with increased tumor size, angiogenesis, and invasiveness, providing the rationale for development of selective COX-2 inhibitors, such as celecoxib [2,3,4,5]. The identification of more selective therapeutic targets downstream of COX-2 signaling has become an important area of ongoing research
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
