Department of Medical and Molecular Genetics, Indiana University School of Medicine, South Bend, IN 46617, USA.
Curr Drug Targets. 2012 Oct;13(11):1445-53. doi: 10.2174/138945012803530215.
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.
杂合性丢失（LOH）在人类染色体 18q 上，其中包括结直肠癌缺失基因（DCC），与结直肠癌和许多其他人类癌症有关。DCC 编码轴突导向分子 Netrin（Net）的受体，并在多种生物体的神经发育过程中发挥作用。然而，自 20 世纪 90 年代发现以来，DCC 作为肿瘤抑制因子的地位一直存在争议，主要是因为在动物模型中缺乏对这一假说的支持。我们实验室最近的一项研究利用果蝇的遗传可操作性，证明了该基因作为一种侵袭性肿瘤抑制因子的功能，从而在癌症动物模型中首次直接将 DCC 缺失与转移表型联系起来。随后其他两个实验室的两项研究表明，DCC 抑制了鼠结直肠癌和乳腺肿瘤模型中的肿瘤进展和转移。这些发现促使 DCC 重新成为肿瘤抑制因子，并强调了在人类癌症的动物模型中继续分析 DCC 功能的必要性。
