title: Strategies of oncogenic microbes to deal with WW domain-containing oxidoreductase.
abstract: WW domain-containing oxidoreductase (WWOX) is a well-documented tumor suppressor protein that controls growth, survival, and metastasis of malignant cells. To counteract WWOX's suppressive effects, cancer cells have developed many strategies either to downregulate WWOX expression or to functionally inactivate WWOX. Relatively unknown is, in the context of those cancers associated with certain viruses or bacteria, how the oncogenic pathogens deal with WWOX. Here we review recent studies showing different strategies utilized by three cancer-associated pathogens. Helicobactor pylori reduces WWOX expression through promoter hypermethylation, an epigenetic mechanism also occurring in many other cancer cells. WWOX has a potential to block canonical NF-κB activation and tumorigenesis induced by Tax, an oncoprotein of human T-cell leukemia virus. Tax successfully overcomes the blockage by inhibiting WWOX expression through activation of the non-canonical NF-κB pathway. On the other hand, latent membrane protein 2A of Epstein-Barr virus physically interacts with WWOX and redirects its function to trigger a signaling pathway that upregulates matrix metalloproteinase 9 and cancer cell invasion. These reports may be just "the tip of the iceberg" regarding multiple interactions between WWOX and oncogenic microbes. Further studies in this direction should expand our understanding of infection-driven oncogenesis.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 70456, Taiwan Graduate Institute of Basic Medical Science, Medical College, National Cheng Kung University, Tainan 70101, Taiwan yaochang@nhri.org.tw.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 70456, Taiwan Graduate Institute of Basic Medical Science, Medical College, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Yu-Yan
authors.initials: YY
authors.lastname: Lan
authors.affiliation: Department of Otolaryngology, Medical College and Hospital, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Jenn-Ren
authors.initials: JR
authors.lastname: Hsiao
authors.affiliation: Institute of Molecular Medicine, Medical College, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Nan-Shan
authors.initials: NS
authors.lastname: Chang
mesh_terms: D063646:Carcinogenesis; D017977:Deltaretrovirus / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D016480:Helicobacter pylori / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D010088:Oxidoreductases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human
keywords: Epstein–Barr virus; Helicobactor pylori; WW domain-containing oxidoreductase; human T-cell leukemia virus; infection-associated cancers