title: Role of WW domain proteins WWOX in development, prognosis, and treatment response of glioma.
abstract: Glioblastoma multiforme (GBM) is the most aggressive and malignant brain tumor. Delicate microenvironment and lineage heterogeneity of GBM cells including infiltration, hypoxia, angiogenesis, and stemness make them highly resistant to current conventional therapies, with an average life expectancy for GBM patients of less than 15 months. Poor response to cytotoxic agents of GBM cells remains the major challenge of GBM treatment. Resistance of GBM to clinical treatment is a result of genomic alternation and deregulated signaling pathways, such as p53 mutation and apoptosis signaling blockage, providing cancer cells more opportunities for survival rather than cell death. WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene, commonly downregulated in various types of tumors, including GBM. It has been found that the reintroduction of WWOX induced p53-mutant GBM cells to undergo apoptosis, but not in p53 wild-type GBM cells, indicating WWOX is likely to reopen apoptosis pathways in a p53-independent manner in GBM. Identifying the crucial target modulated by WWOX deficiency provides a potential therapeutic target for GBM treatment. Here, we have reviewed the literatures about the role of WWOX in development, signaling pathway, prognosis, and treatment response in malignant glioma.
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: Shin-Yi
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Mackay Memorial Hospital, Taipei 104, Taiwan Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei 110, Taiwan chiang66@gmail.com chenmdphd@gmail.com.
authors.forename: Ming-Fu
authors.initials: MF
authors.lastname: Chiang
authors.affiliation: Department of Radiation Oncology, Mackay Memorial Hospital, Taipei 104, Taiwan Graduate Institute of Pharmacology, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D005909:Glioblastoma / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D009154:Mutation / Q000235:genetics; D010088:Oxidoreductases / Q000502:physiology*; D011379:Prognosis; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / 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: WW domain-containing oxidoreductase; glioma; p53; resistance