• cancer

The human gene WWOX has been described as a tumor suppressor gene, but its function is not understood. It encodes a member of the short-chain dehydrogenases/reductases (SDR) protein family; the encoded protein may play a role in reactive oxygen species regulation and metabolic homeostasis. There is a single orthologous gene in Drosophila, Dmel\Wwox, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and an amorphic allele created by targeted recombination have been generated.

A UAS construct of the wild-type human Hsap\WWOX gene has been introduced into flies, but has not been characterized in the context of this disease model.

Animals that are homozygous for an amorphic mutation of Dmel\Wwox are viable, without conspicuous visible phenotypes. A phenotype of sensitivity to ionizing radiation has been described, but was subsequently found to be due to genetic background. A small number of genetic interactions have been reported for Dmel\Wwox; see the Wwox gene report.

In several assays, reductions in the expression of Wwox in concert with other tumorigenic changes result in an increase in overgrowth phenotypes. Decreased Wwox expression exacerbates the overgrowth-related phenotypes caused by reduced expression of a number of different mitochondrial respiratory complex genes (assayed as RNAi-effected phenotypes in the adult eye). In a model of cell overgrowth using clones of scrib mutant cells in the developing eye disc (see FBhh0000587), tumorigenic clones that are surrounded by wild-type cells are eliminated or reduced in size; a decrease of Wwox within the clones of tumorigenic cells disrupts this process, resulting in an increase in their ability to compete and a decrease in their elimination.

[updated Feb. 2019 by FlyBase; FBrf0222196]