%0 Journal Article %T The Drosophila Netrin receptor frazzled/DCC functions as an invasive tumor suppressor %A Adrienne VanZomeren-Dohm %A Joseph Sarro %A Ellen Flannery %A Molly Duman-Scheel %J BMC Developmental Biology %D 2011 %I BioMed Central %R 10.1186/1471-213x-11-41 %X Most fra loss of function clones are eliminated during development. However, when mutant clone cells generated in the developing eye were rescued from death, partially differentiated eye cells were found outside of the normal eye field, and in extreme cases distant sites of the body. Characterization of these cells during development indicates that fra mutant cells display characteristics of invasive tumor cells, including increased levels of phospho-ERK, phospho-JNK, and Mmp-1, changes in cadherin expression, remodeling of the actin cytoskeleton, and loss of polarity. Mutation of fra promotes basement membrane degradation and invasion which are repressed by inhibition of Rho1 signaling. Although inhibition of JNK signaling blocks invasive phenotypes in some metastatic cancer models in flies, blocking JNK signaling inhibits fra mutant cell death, thereby enhancing the fra mutant phenotype.The results of this investigation provide the first direct link between point mutations in fra/DCC and metastatic phenotypes in an animal model and suggest that Fra functions as an invasive tumor suppressor during Drosophila development.Loss of heterozygosity (LOH) at chromosome 18q, which includes the DCC gene, was identified in a large percentage of colorectal cancers [1]. LOH at 18q is associated with decreased DCC expression and has been linked to many other types of cancer, including neuroblastomas, hematologic malignancies, and gastric, endometrial, prostate, ovarian, esophageal, testicular, breast, and glial cancers [2,3]. It was therefore hypothesized that DCC functions as a tumor suppressor. However, although elevated levels of the DCC ligand Netrin (Net) have been linked to oncogenic phenotypes [4,5], point mutations in DCC have not been directly associated with tumorigenesis in animal models [2]. For example, loss of DCC is not associated with tumor formation in a murine model [6]. However, although the impact of mutating DCC in every cell of an organism has been investi %U http://www.biomedcentral.com/1471-213X/11/41