Four jointed box 1 promotes angiogenesis and is associated with poor patient survival in colorectal carcinoma.
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.
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, United States of America.
Nicole T
NT
Al-Greene
Anna L
AL
Means
Pengcheng
P
Lu
Aixiang
A
Jiang
Carl R
CR
Schmidt
A Bapsi
AB
Chakravarthy
Nipun B
NB
Merchant
M Kay
MK
Washington
Bing
B
Zhang
Yu
Y
Shyr
Natasha G
NG
Deane
R Daniel
RD
Beauchamp
D000818:Animals; D001397:Azoxymethane / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016264:Dextran Sulfate / Q000627:therapeutic use; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D016264:Dextran Sulfate; D001397:Azoxymethane