Loss of heterozygosity (LOH) at human chromosome 18q, which includes the gene Deleted in Colorectal Cancer
(DCC), has been linked to colorectal and many other human cancers. DCC encodes the receptor for the axon guidance
molecule Netrin (Net) and functions during neural development in a variety of organisms. However, since its discovery in
the 1990s, the status of DCC as a tumor suppressor has been debated, primarily due to a lack of support for this hypothesis
in animal models. A recent study from our laboratory capitalized on the genetic tractability of Drosophila melanogaster to
demonstrate that this gene functions as an invasive tumor suppressor, thereby providing the first direct link between DCC
loss and metastatic phenotypes in an animal model for cancer. Two subsequent studies from other laboratories have demonstrated
that DCC suppresses tumor progression and metastasis in murine colorectal and mammary tumor models. Combined,
these findings have prompted the rebirth of DCC as a tumor suppressor and highlighted the need for continued
analysis of DCC function in animal models for human cancer.
Keywords: Apoptosis, axon guidance, cancer, DCC, Drosophila melanogaster, metastasis, netrin, tumor suppressor, LOH, metastatic phenotype.
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