The WW domain-containing oxidoreductase (WWOX) spans one of the most active common fragile sites (CFSs) involved in cancer, FRA16D. WWOX encodes a 46-kDa protein that contains two N-terminal WW domains and a central short-chain dehydrogenase/reductase (SDR) domain. Through its WW domain, Wwox interacts with its partners and modulates their functions. Our data indicate that Wwox suppresses the transactivation function of several transcription factors implied in neoplasia by sequestering them in the cytoplasm. Work from our laboratory and other research groups have demonstrated that Wwox participates in a number of cellular processes including growth, differentiation, apoptosis, and tumor suppression. Targeted deletion of the Wwox gene in mice causes increased spontaneous and chemically induced tumor incidence supporting bona fide tumor suppressor function of WWOX. Moreover, generation of the Wwox-deficient mice uncovers, at least in part, some of the physiological in vivo functions of the WWOX gene. This review focuses on recent progress that elucidates Wwox functions in biology and pathology.
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Article Synopsis
- WWOX developmental and epileptic encephalopathy (DEE) typically starts in infancy and leads to severe developmental delays and drug-resistant epilepsy.
- This report details a unique case of an adult patient with a rare genetic variant who experienced various types of seizures and significant regression in motor skills over his life.
- The case highlights the importance of early genetic testing in diagnosing developmental and epileptic conditions, aiding in proper identification and management of similar patients.
WWOX tuning of oleic acid signaling orchestrates immunosuppressive macrophage polarization and sensitizes hepatocellular carcinoma to immunotherapy.
J Immunother Cancer
November 2024
Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
Background: Immune checkpoint inhibitors (ICIs) are therapeutically effective for hepatocellular carcinoma (HCC) but are individually selective. This study examined the role of specific common fragile sites (CFSs) related gene in HCC immunotherapy.
Methods: We analyzed HCC tissues using next-generation sequencing and flow cytometry via time-of-flight technology.
Loss of WWOX contributes to cisplatin resistance in triple-negative breast cancer cells by modulating miR-182 and miR-214.
Turk J Med Sci
October 2024
Department of Computer Sciences and Communication, Faculty of Computer Sciences, Østfold University College, Halden, Norway.
Background/aim: WW domain-containing oxidoreductase (WWOX) loss frequently occurs in triple-negative breast cancer (TNBC). WWOX loss enhances cisplatin resistance in TNBC patients. Although WWOX loss has an effect on the selection of a DNA repair pathway that contributes to enhanced mutagenesis, the downstream expression changes in resistant cancer cells have not been fully explored.
View Article and Find Full Text PDFDissociation of the nuclear WWOX/TRAF2 switch renders UV/cold shock-mediated nuclear bubbling cell death at low temperatures.
Cell Commun Signal
October 2024
Institute of Molecular Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
Background: Normal cells express functional tumor suppressor WW domain-containing oxidoreductase (WWOX), designated WWOXf. UV irradiation induces WWOXf cells to undergo bubbling cell death (BCD) - an event due to the accumulation of nuclear nitric oxide (NO) gas that forcefully pushes the nuclear and cell membranes to form one or two bubbles at room temperature (22 °C) and below. In contrast, when WWOX-deficient or -dysfunctional (WWOXd) cells are exposed to UV and/or cold shock, the cells undergo nuclear pop-out explosion death (POD).
View Article and Find Full Text PDF-related epileptic encephalopathy caused by a novel mutation in the gene: a case report.
Front Pediatr
October 2024
Department of Neonatology, Lanzhou University Second Hospital, Lanzhou, China.
Article Synopsis
- The text discusses an autosomal recessive disorder related to epilepsy caused by mutations in the WW-containing oxidoreductase gene, leading to severe seizures and developmental issues in infants.
- A case study of a 5-month-old boy showcases intractable seizures, developmental delays, and a newly identified mutation that was inherited from his healthy parents.
- The findings highlight the importance of discovering new gene variants, which could improve the understanding and treatment options for related disorders.
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