title: Regulation of cell signaling and apoptosis by tumor suppressor WWOX.
abstract: Human fragile WWOX gene encodes a tumor suppressor WW domain-containing oxidoreductase (named WWOX, FOR, or WOX1). Functional suppression of WWOX prevents apoptotic cell death induced by a variety of stress stimuli, such as tumor necrosis factor, UV radiation, and chemotherapeutic drug treatment. Loss of WWOX gene expression due to gene deletions, loss of heterozygosity, chromosomal translocations, or epigenetic silencing is frequently observed in human malignant cancer cells. Acquisition of chemoresistance in squamous cell carcinoma, osteosarcoma, and breast cancer cells is associated with WWOX deficiency. WWOX protein physically interacts with many signaling molecules and exerts its regulatory effects on gene transcription and protein stability and subcellular localization to control cell survival, proliferation, differentiation, autophagy, and metabolism. In this review, we provide an overview of the recent advances in understanding the molecular mechanisms by which WWOX regulates cellular functions and stress responses. A potential scenario is that activation of WWOX by anticancer drugs is needed to overcome chemoresistance and trigger cancer cell death, suggesting that WWOX can be regarded as a prognostic marker and a candidate molecule for targeted cancer therapies.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
authors.forename: Jui-Yen
authors.initials: JY
authors.lastname: Lo
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
authors.forename: Ying-Tsen
authors.initials: YT
authors.lastname: Chou
authors.affiliation: Department of Dermatology, Chimei Medical Center, Tainan 71004, Taiwan.
authors.forename: Feng-Jie
authors.initials: FJ
authors.lastname: Lai
authors.affiliation: Department of Medical Laboratory Science and Biotechnology Center of Infectious Disease and Signaling Research and Research Center for Medical Laboratory Biotechnology, National Cheng Kung University Medical College, Tainan 70101, Taiwan lijin.hsu@gmail.com.
authors.forename: Li-Jin
authors.initials: LJ
authors.lastname: Hsu
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D010088:Oxidoreductases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human
keywords: Tumor suppressor; apoptosis; chemoresistance; signal transduction; transcription factor