WWOX (WW domain containing oxidoreductase) protein is a candidate tumor suppressor consisting of two WW domains that influence protein-protein interactions, and a short chain dehydrogenase (SDR) domain, that influences sex-steroid metabolism. Modulation of the WWOX gene influences esophageal squamous cell carcinogenesis and tumorigenicity of breast cancer cell lines MDA-MB-435 and T47D. The murine homolog WOX1 localizes in the mitochondria, and contains a mitochondrial targeting sequence mapping within the SDR domain. JNK1 can physically associate with WOX1 and sequester WOX1-dependent apoptosis.