Functional Characterization Of Filamin A Interacting Protein 1-Like, A Novel Candidate For Antivascular Cancer Therapy

Inhibiting angiogenesis has become a major therapeutic strategy for cancer treatment. To identify common intracellular mediators, we previously analyzed gene expression profiles of endothelial cells after treatment with angiogenesis inhibitors. Filamin A interacting protein 1-like (FILIPIL; previously known as down-regulated in ovarian concert) was identified as one of the genes up-regulated in endothelial cells in response to these inhibitors. However, the expression and function of FILIPIL protein is uncharacterized. Here, we provide the first description of the expression and specific subcellular localization of FILIPIL protein in human tissue. Overexpression of FILIPIL resulted in inhibition of cell proliferation and migration and increased apoptosis. In addition, overexpression of FILIPIL truncation mutants showed differential antiproliferative activity. A COOH terminal truncation mutant (FILIP1L Delta C103) was more potent than wild-type FILIPIL in mediating this activity. Targeted expression of FILIP1L Delta C103 in tumor vasculature inhibited tumor growth in vivo. Overall, these findings suggest that the novel protein FILIPIL may be an important mediator of the effects of angiogenesis inhibitors and that FILIPIL, has the potential to be an antivascular reagent for cancer therapy.