WWOX

Summary

Gene Symbol: WWOX
Description: WW domain containing oxidoreductase
Alias: D16S432E, EIEE28, FOR, FRA16D, HHCMA56, PRO0128, SCAR12, SDR41C1, WOX1, WW domain-containing oxidoreductase, WW domain-containing protein WWOX, fragile site FRA16D oxidoreductase, short chain dehydrogenase/reductase family 41C member 1
Species: human
Products:     WWOX

Top Publications

  1. Lee J, Weissglas Volkov D, Kyttälä M, Dastani Z, Cantor R, Sobel E, et al. WW-domain-containing oxidoreductase is associated with low plasma HDL-C levels. Am J Hum Genet. 2008;83:180-92 pubmed publisher
    ..We identified one SNP, rs2548861, in the WW-domain-containing oxidoreductase (WWOX) gene with region-wide significance for low HDL-C in dyslipidemic families of Mexican and European descent and in ..
  2. Lai F, Cheng C, Chen S, Wu C, Hsu L, Lee J, et al. WOX1 is essential for UVB irradiation-induced apoptosis and down-regulated via translational blockade in UVB-induced cutaneous squamous cell carcinoma in vivo. Clin Cancer Res. 2005;11:5769-77 pubmed
    We investigated the role of candidate tumor suppressor and proapoptotic WOX1 (also named WWOX, FOR, or WWOXv1) in UVB-induced apoptosis and formation of cutaneous squamous cell carcinomas (SCC)...
  3. Ramos D, Abba M, Lopez Guerrero J, Rubio J, Solsona E, Almenar S, et al. Low levels of WWOX protein immunoexpression correlate with tumour grade and a less favourable outcome in patients with urinary bladder tumours. Histopathology. 2008;52:831-9 pubmed publisher
    To correlate the immunohistochemical detection of WWOX with histological measures and disease progression within the whole spectrum of urothelial bladder neoplasms...
  4. Aqeilan R, Donati V, Palamarchuk A, Trapasso F, Kaou M, Pekarsky Y, et al. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res. 2005;65:6764-72 pubmed
    The WW domain-containing oxidoreductase, WWOX, is a tumor suppressor that is deleted or altered in several cancer types. We recently showed that WWOX interacts with p73 and AP-2gamma and suppresses their transcriptional activity...
  5. Chang N, Pratt N, Heath J, Schultz L, Sleve D, Carey G, et al. Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity. J Biol Chem. 2001;276:3361-70 pubmed
    ..here the isolation and characterization of a hyaluronidase-induced murine WW domain-containing oxidoreductase (WOX1)...
  6. Aderca I, Moser C, Veerasamy M, Bani Hani A, Bonilla Guerrero R, Ahmed K, et al. The JNK inhibitor SP600129 enhances apoptosis of HCC cells induced by the tumor suppressor WWOX. J Hepatol. 2008;49:373-83 pubmed publisher
    The FRA16D fragile site gene WWOX is a tumor suppressor that participates in p53-mediated apoptosis. The c-jun N-terminal kinase JNK1 interacts with WWOX and inhibits apoptosis...
  7. Donati V, Fontanini G, Dell Omodarme M, Prati M, Nuti S, Lucchi M, et al. WWOX expression in different histologic types and subtypes of non-small cell lung cancer. Clin Cancer Res. 2007;13:884-91 pubmed
    ..b>WWOX (WW domain-containing oxidoreductase) is a tumor suppressor gene, and its expression is altered in several cancers...
  8. Chang N, Schultz L, Hsu L, Lewis J, Su M, Sze C. 17beta-Estradiol upregulates and activates WOX1/WWOXv1 and WOX2/WWOXv2 in vitro: potential role in cancerous progression of breast and prostate to a premetastatic state in vivo. Oncogene. 2005;24:714-23 pubmed
    Human WWOX gene encodes a proapoptotic WW domain-containing oxidoreductase WOX1 (also named WWOX, FOR2 or WWOXv1). Apoptotic and stress stimuli activate WOX1 via Tyr33 phosphorylation and nuclear translocation...
  9. Park S, Ludes Meyers J, Zimonjic D, Durkin M, Popescu N, Aldaz C. Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma. Br J Cancer. 2004;91:753-9 pubmed
    ..tumour suppressor gene spanning the same chromosome region, 16q23, as the second most common fragile site (FS), FRA16D. Deletions detected by comparative genomic hybridisation (CGH) and loss of heterozygosity at microsatellite ..

More Information

Publications83

  1. Paige A, Zucknick M, Janczar S, Paul J, Mein C, Taylor K, et al. WWOX tumour suppressor gene polymorphisms and ovarian cancer pathology and prognosis. Eur J Cancer. 2010;46:818-25 pubmed publisher
    b>WWOX is a bona fide tumour suppressor, with hypomorphic and knockout mouse models exhibiting increased tumour susceptibility...
  2. Gaudio E, Palamarchuk A, Palumbo T, Trapasso F, Pekarsky Y, Croce C, et al. Physical association with WWOX suppresses c-Jun transcriptional activity. Cancer Res. 2006;66:11585-9 pubmed
    b>WWOX is a tumor suppressor that functions as a modular protein partner of transcription factors. WWOX contains two WW domains that mediate protein-protein interactions...
  3. Liu C, Shen W, Peng S, Cheng H, Kao S, Lin S, et al. miR-134 induces oncogenicity and metastasis in head and neck carcinoma through targeting WWOX gene. Int J Cancer. 2014;134:811-21 pubmed publisher
    ..In situ hybridization and immunohistochemistry were used to detect the expression of miR-134 and the WWOX gene in human HNSCC. The results indicated that miR-134 was upregulated in HNSCC tissues relative to control mucosa...
  4. Salah Z, Aqeilan R, Huebner K. WWOX gene and gene product: tumor suppression through specific protein interactions. Future Oncol. 2010;6:249-59 pubmed publisher
    The WWOX gene, an archetypal fragile gene, encompasses a chromosomal fragile site at 16q23.2, and encodes the approximately 46-kDa Wwox protein, with WW domains that interact with a growing list of interesting proteins...
  5. Ramos D, Aldaz C. WWOX, a chromosomal fragile site gene and its role in cancer. Adv Exp Med Biol. 2006;587:149-59 pubmed
    ..3-24.1 (FRA16D: the second most active common chromosomal fragile site in the human genome)...
  6. Mahajan N, Whang Y, Mohler J, Earp H. Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer Res. 2005;65:10514-23 pubmed
    ..Further, we identify the tumor suppressor WW domain containing oxidoreductase (Wwox) as an Ack1-interacting protein...
  7. Kuroki T, Yendamuri S, Trapasso F, Matsuyama A, Aqeilan R, Alder H, et al. The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis. Clin Cancer Res. 2004;10:2459-65 pubmed
    WWOX (WW domain containing oxidoreductase) is a tumor suppressor gene that maps to the common fragile site FRA16D. We showed previously that WWOX is frequently altered in human lung and esophageal cancers...
  8. Wang H, Juo L, Lin Y, Hsiao M, Lin J, Tsai C, et al. WW domain-containing oxidoreductase promotes neuronal differentiation via negative regulation of glycogen synthase kinase 3?. Cell Death Differ. 2012;19:1049-59 pubmed publisher
    WW domain-containing oxidoreductase (WWOX), a putative tumour suppressor, is suggested to be involved in the hyperphosphorylation of Alzheimer's Tau...
  9. Yang J, Cogdell D, Yang D, Hu L, Li H, Zheng H, et al. Deletion of the WWOX gene and frequent loss of its protein expression in human osteosarcoma. Cancer Lett. 2010;291:31-8 pubmed publisher
    To evaluate the role of WWOX gene in human osteosarcoma, array comparative genomic hybridization on 10 frozen osteosarcoma specimens and immunohistochemical staining of 55 formalin-fixed and paraffin-embedded tissues for WWOX was ..
  10. Iliopoulos D, Guler G, Han S, Johnston D, Druck T, McCorkell K, et al. Fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancer. Oncogene. 2005;24:1625-33 pubmed
    This study aimed to (a) determine if DNA methylation is a mechanism of WWOX (WW domain containing oxidoreductase) and FHIT (fragile histidine triad) inactivation in lung, breast and bladder cancers; (b) examine distinct methylation ..
  11. Guler G, Huebner K, Himmetoglu C, Jimenez R, Costinean S, Volinia S, et al. Fragile histidine triad protein, WW domain-containing oxidoreductase protein Wwox, and activator protein 2gamma expression levels correlate with basal phenotype in breast cancer. Cancer. 2009;115:899-908 pubmed publisher
    ..oxidoreductase protein (Wwox), tumor suppressors that are encoded by fragile (FRA) loci FRA3B and FRA16D, are lost concordantly in breast cancers...
  12. Ludes Meyers J, Bednarek A, Popescu N, Bedford M, Aldaz C. WWOX, the common chromosomal fragile site, FRA16D, cancer gene. Cytogenet Genome Res. 2003;100:101-10 pubmed
    ..dissection of this region resulting in the cloning of the putative tumor suppressor gene, WWOX (WW domain containing Oxidoreductase)...
  13. Sze C, Su M, Pugazhenthi S, Jambal P, Hsu L, Heath J, et al. Down-regulation of WW domain-containing oxidoreductase induces Tau phosphorylation in vitro. A potential role in Alzheimer's disease. J Biol Chem. 2004;279:30498-506 pubmed
    ..age-matched normal controls, we demonstrated here that the protein levels of WW domain-containing oxidoreductase WOX1 (also known as WWOX or FOR), its Tyr33-phosphorylated form, and WOX2 were significantly down-regulated in the ..
  14. Maeda N, Semba S, Nakayama S, Yanagihara K, Yokozaki H. Loss of WW domain-containing oxidoreductase expression in the progression and development of gastric carcinoma: clinical and histopathologic correlations. Virchows Arch. 2010;457:423-32 pubmed publisher
    ..the role of the WW domain-containing oxidoreductase (WWOX) tumor suppressor that maps to the common fragile site FRA16D (16q23.3-24...
  15. Abdeen S, Salah Z, Maly B, Smith Y, Tufail R, Abu Odeh M, et al. Wwox inactivation enhances mammary tumorigenesis. Oncogene. 2011;30:3900-6 pubmed publisher
    Breast cancer is the leading cause of cancer-related death in women worldwide. Expression of the WWOX tumor suppressor is absent or reduced in a large proportion of breast tumors suggesting that loss of WWOX may contribute to breast ..
  16. Bednarek A, Keck Waggoner C, Daniel R, Laflin K, Bergsagel P, Kiguchi K, et al. WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. Cancer Res. 2001;61:8068-73 pubmed
    We recently reported the cloning of WWOX, a gene that maps to the common fragile site FRA16D region in chromosome 16q23.3-24.1...
  17. Hu B, Tan J, Zhu G, Wang D, Zhou X, Sun Z. WWOX induces apoptosis and inhibits proliferation of human hepatoma cell line SMMC-7721. World J Gastroenterol. 2012;18:3020-6 pubmed publisher
    To investigate the effects of the WWOX gene on the human hepatic carcinoma cell line SMMC-7721. Full-length WWOX cDNA was amplified from normal human liver tissues...
  18. Lo C, Hsu L, Li M, Hsu S, Chuang J, Tsai M, et al. MPP+-induced neuronal death in rats involves tyrosine 33 phosphorylation of WW domain-containing oxidoreductase WOX1. Eur J Neurosci. 2008;27:1634-46 pubmed publisher
    WW domain-containing oxidoreductase (named WWOX, FOR or WOX1) is a pro-apoptotic protein and tumor suppressor. Animals treated with dopaminergic neurotoxin 1-methyl-4-phenyl-pyridinium (MPP+) develop Parkinson's disease (PD)-like symptoms...
  19. Baykara O, Demirkaya A, Kaynak K, Tanju S, Toker A, Buyru N. WWOX gene may contribute to progression of non-small-cell lung cancer (NSCLC). Tumour Biol. 2010;31:315-20 pubmed publisher
    ..The WW domain-containing oxidoreductase (WWOX) gene is a tumor-suppressor gene located on chromosome 16q23.3-24...
  20. Gourley C, Paige A, Taylor K, Ward C, Kuske B, Zhang J, et al. WWOX gene expression abolishes ovarian cancer tumorigenicity in vivo and decreases attachment to fibronectin via integrin alpha3. Cancer Res. 2009;69:4835-42 pubmed publisher
    The WW domain-containing oxidoreductase (WWOX) gene is located at FRA16D, a common fragile site involved in human cancer...
  21. Płuciennik E, Kusinska R, Potemski P, Kubiak R, Kordek R, Bednarek A. WWOX--the FRA16D cancer gene: expression correlation with breast cancer progression and prognosis. Eur J Surg Oncol. 2006;32:153-7 pubmed
    ..gene covers approximately 1 million base pairs of the second most affected among common chromosomal fragile sites FRA16D. We evaluated WWOX expression levels in breast cancer samples in association with diagnostics-prognostics markers...
  22. Hsu L, Schultz L, Hong Q, Van Moer K, Heath J, Li M, et al. Transforming growth factor beta1 signaling via interaction with cell surface Hyal-2 and recruitment of WWOX/WOX1. J Biol Chem. 2009;284:16049-59 pubmed publisher
    ..This binding resulted in recruitment of proapoptotic WOX1 (also named WWOX or FOR) and formation of Hyal-2.WOX1 complexes for relocation to the nuclei...
  23. Roy D, Sin S, Damania B, Dittmer D. Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines. Blood. 2011;118:e32-9 pubmed publisher
    ..Eleven of 13 samples (85%) were deleted for the fragile site tumor suppressors WWOX and FHIT...
  24. Pimenta F, Gomes D, Perdigão P, Barbosa A, Romano Silva M, Gomez M, et al. Characterization of the tumor suppressor gene WWOX in primary human oral squamous cell carcinomas. Int J Cancer. 2006;118:1154-8 pubmed
    ..3-24.1, spanning the second most common fragile site, FRA16D. In this report, the role of the WWOX gene was investigated in 20 tumors and 10 normal oral mucosas, and we ..
  25. Aqeilan R, Hassan M, de Bruin A, Hagan J, Volinia S, Palumbo T, et al. The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism. J Biol Chem. 2008;283:21629-39 pubmed publisher
    The WW domain-containing oxidoreductase (WWOX) gene encodes a tumor suppressor. We have previously shown that targeted ablation of the Wwox gene in mouse increases the incidence of spontaneous and chemically induced tumors...
  26. Chang N, Doherty J, Ensign A. JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis. J Biol Chem. 2003;278:9195-202 pubmed
    ..PH-20 also induces the expression of a p53-interacting WW domain-containing oxidoreductase (WOX1, also known as WWOX or FOR) in these cells...
  27. Dayan S, O Keefe L, Choo A, Richards R. Common chromosomal fragile site FRA16D tumor suppressor WWOX gene expression and metabolic reprograming in cells. Genes Chromosomes Cancer. 2013;52:823-31 pubmed publisher
    The WWOX gene spans the FRA16D common chromosomal fragile site and is able to suppress tumor growth. FRA16D is a frequent site of DNA instability in cancer resulting in reduced levels of WWOX expression...
  28. Zelazowski M, Płuciennik E, Pasz Walczak G, Potemski P, Kordek R, Bednarek A. WWOX expression in colorectal cancer--a real-time quantitative RT-PCR study. Tumour Biol. 2011;32:551-60 pubmed publisher
    The WWOX gene is a tumour suppressor gene affected in various types of malignancies. Numerous studies showed either loss or reduction of the WWOX expression in variety of tumours, including breast, ovary, liver, stomach and pancreas...
  29. Guler G, Uner A, Guler N, Han S, Iliopoulos D, Hauck W, et al. The fragile genes FHIT and WWOX are inactivated coordinately in invasive breast carcinoma. Cancer. 2004;100:1605-14 pubmed
    FHIT and WWOX are a tumor suppressor and a candidate suppressor that encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3-24.1, respectively...
  30. Paige A, Taylor K, Taylor C, Hillier S, Farrington S, Scott D, et al. WWOX: a candidate tumor suppressor gene involved in multiple tumor types. Proc Natl Acad Sci U S A. 2001;98:11417-22 pubmed
    ..Using these PAC clones in a cDNA selection experiment, we have isolated a Sau3A fragment homologous to the WWOX transcript (GenBank accession no. ) from normal human ovarian surface epithelial (HOSE) cells...
  31. Aqeilan R, Donati V, Gaudio E, Nicoloso M, Sundvall M, Korhonen A, et al. Association of Wwox with ErbB4 in breast cancer. Cancer Res. 2007;67:9330-6 pubmed
    b>WWOX, WW domain-containing oxidoreductase, is a tumor suppressor that is altered in many human cancers, including breast cancer...
  32. Fabbri M, Iliopoulos D, Trapasso F, Aqeilan R, Cimmino A, Zanesi N, et al. WWOX gene restoration prevents lung cancer growth in vitro and in vivo. Proc Natl Acad Sci U S A. 2005;102:15611-6 pubmed
    The WWOX (WW domain containing oxidoreductase) gene at the common fragile site, FRA16D, is altered in many types of cancer, including lung cancer. We have examined the tumor suppressor function of WWOX in preclinical lung cancer models...
  33. Cancemi L, Romei C, Bertocchi S, Tarrini G, Spitaleri I, Cipollini M, et al. Evidences that the polymorphism Pro-282-Ala within the tumor suppressor gene WWOX is a new risk factor for differentiated thyroid carcinoma. Int J Cancer. 2011;129:2816-24 pubmed publisher
    ..rs3764340 encoding for the aminoacidic substitution proline-to-alanine at codon 282 of the tumor suppressor gene WWOX, passed the selection...
  34. Watanabe A, Hippo Y, Taniguchi H, Iwanari H, Yashiro M, Hirakawa K, et al. An opposing view on WWOX protein function as a tumor suppressor. Cancer Res. 2003;63:8629-33 pubmed
    WW domain-containing oxidoreductase (WWOX) is a candidate tumor suppressor gene...
  35. Jin C, Ge L, Ding X, Chen Y, Zhu H, Ward T, et al. PKA-mediated protein phosphorylation regulates ezrin-WWOX interaction. Biochem Biophys Res Commun. 2006;341:784-91 pubmed
    ..we provide the first evidence that PKA-mediated phosphorylation of Ser(66)regulates the interaction of ezrin with WWOX, a WW domain-containing protein...
  36. McDonald C, Buffa L, Bar Mag T, Salah Z, Bhat V, Mikles D, et al. Biophysical basis of the binding of WWOX tumor suppressor to WBP1 and WBP2 adaptors. J Mol Biol. 2012;422:58-74 pubmed publisher
    The WW-containing oxidoreductase (WWOX) tumor suppressor participates in a diverse array of cellular activities by virtue of its ability to recognize WW-binding protein 1 (WBP1) and WW-binding protein 2 (WBP2) signaling adaptors among a ..
  37. Ludes Meyers J, Kil H, Bednarek A, Drake J, Bedford M, Aldaz C. WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins. Oncogene. 2004;23:5049-55 pubmed
    WWOX, the gene that maps to common chromosomal fragile site FRA16D, is frequently affected by aberrations in multiple types of cancers...
  38. Aqeilan R, Pekarsky Y, Herrero J, Palamarchuk A, Letofsky J, Druck T, et al. Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proc Natl Acad Sci U S A. 2004;101:4401-6 pubmed
    The WWOX gene is a recently cloned tumor suppressor gene that spans the FRA16D fragile region. Wwox protein contains two WW domains that are generally known to mediate protein-protein interaction...
  39. Aqeilan R, Palamarchuk A, Weigel R, Herrero J, Pekarsky Y, Croce C. Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2gamma transcription factor. Cancer Res. 2004;64:8256-61 pubmed
    The WWOX gene encodes a tumor suppressor WW domain-containing protein, Wwox...
  40. Zhou Y, Li Y, Shou F, Liu C, Pu Y, Tang H. Reversing effect of exogenous WWOX gene expression on malignant phenotype of primary cultured lung carcinoma cells. Chin Med J (Engl). 2010;123:615-20 pubmed
    Whether WW domain containing oxidoreductase (WWOX) gene is a tumor-suppressor is still controversial...
  41. Kuroki T, Trapasso F, Shiraishi T, Alder H, Mimori K, Mori M, et al. Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma. Cancer Res. 2002;62:2258-60 pubmed
    The WWOX (WW domain containing oxidoreductase) gene was recently identified as a candidate tumor suppressor gene at 16q23.3-24.1, a chromosome region that spans the common fragile site FRA16D...
  42. Alsop A, Taylor K, Zhang J, Gabra H, Paige A, Edwards P. Homozygous deletions may be markers of nearby heterozygous mutations: The complex deletion at FRA16D in the HCT116 colon cancer cell line removes exons of WWOX. Genes Chromosomes Cancer. 2008;47:437-47 pubmed publisher
    ..rearrangements that have targets outside the homozygous deletion itself and that the target of deletions in the FRA16D region is indeed WWOX, the common outcome being the removal of particular WWOX exons...
  43. Guler G, Iliopoulos D, Guler N, Himmetoglu C, Hayran M, Huebner K. Wwox and Ap2gamma expression levels predict tamoxifen response. Clin Cancer Res. 2007;13:6115-21 pubmed
    Assessment of expression levels of Wwox, Wwox-interacting proteins Ap2alpha, Ap2gamma, and ErbB4, the Ap2gamma transcriptional target protein Her2, and the possible Ap2alpha transcriptional target PrkaRIalpha, in breast cancers, to ..
  44. Yang L, Liu B, Huang B, Deng J, Li H, Yu B, et al. A functional copy number variation in the WWOX gene is associated with lung cancer risk in Chinese. Hum Mol Genet. 2013;22:1886-94 pubmed publisher
    ..WWOX maps to the common chromosomal fragile site FRA16D and several copy number variations (CNVs) were found within this gene...
  45. Nakayama S, Semba S, Maeda N, Aqeilan R, Huebner K, Yokozaki H. Role of the WWOX gene, encompassing fragile region FRA16D, in suppression of pancreatic carcinoma cells. Cancer Sci. 2008;99:1370-6 pubmed publisher
    The WW-domain-containing oxidoreductase (WWOX) gene spans the common chromosomal fragile site FRA16D (16q23.2) and is believed to be a tumor suppressor in various human malignancies...
  46. Lan C, Chenggang W, Yulan B, Xiaohui D, Junhui Z, Xiao W. Aberrant expression of WWOX protein in epithelial ovarian cancer: a clinicopathologic and immunohistochemical study. Int J Gynecol Pathol. 2012;31:125-32 pubmed publisher
    ..3-24.1, a region that spans the second most common human fragile site, FRA16D. Abnormalities affecting WWOX at the genomic and/or expression level(s) have been reported in numerous neoplasias ..
  47. Salah Z, Bar mag T, Kohn Y, Pichiorri F, Palumbo T, Melino G, et al. Tumor suppressor WWOX binds to ?Np63? and sensitizes cancer cells to chemotherapy. Cell Death Dis. 2013;4:e480 pubmed publisher
    The WWOX tumor suppressor is a WW domain-containing protein. Its function in the cell has been shown to be mediated, in part, by interacting with its partners through its first WW (WW1) domain...
  48. Xiong Z, Hu S, Wang Z. Cloning of WWOX gene and its growth-inhibiting effects on ovarian cancer cells. J Huazhong Univ Sci Technolog Med Sci. 2010;30:365-9 pubmed publisher
    The growth-inhibiting and apoptosis-inducing effects of WW domain-containing oxidoreductase (WWOX) gene on ovarian cancer cell line A2780 were investigated...
  49. Lin J, Tzai T, Liao C, Wang J, Wu T, Wang H, et al. WWOX protein expression varies among RCC histotypes and downregulation of WWOX protein correlates with less-favorable prognosis in clear RCC. Ann Surg Oncol. 2013;20:193-9 pubmed publisher
    b>WWOX has been shown to be a candidate tumor suppressor gene in numerous human cancers...
  50. Bednarek A, Laflin K, Daniel R, Liao Q, Hawkins K, Aldaz C. WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer. Cancer Res. 2000;60:2140-5 pubmed
    ..We speculate that WWOX may span the yet uncharacterized common fragile site FRA16D region...
  51. Kurek K, Del Mare S, Salah Z, Abdeen S, Sadiq H, Lee S, et al. Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression. Cancer Res. 2010;70:5577-86 pubmed publisher
    The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is deleted or attenuated in most human tumors...
  52. Bouteille N, Driouch K, Hage P, Sin S, Formstecher E, Camonis J, et al. Inhibition of the Wnt/beta-catenin pathway by the WWOX tumor suppressor protein. Oncogene. 2009;28:2569-80 pubmed publisher
    The WWOX gene encodes a candidate tumor suppressor protein (WWOX) implicated in a variety of human diseases such as cancer. To better understand the molecular mechanisms of WWOX action, we investigated novel partners of this protein...
  53. Ishii H, Mimori K, Vecchione A, Sutheesophon K, Fujiwara T, Mori M, et al. Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX. Biochem Biophys Res Commun. 2004;316:1088-93 pubmed
    The expression of two tumor suppressor genes, fragile histidine triad (FHIT) and WW domain containing oxidoreductase (WWOX), encompassing common chromosome fragile regions, FRA3B at 3p14...
  54. Qin H, Iliopoulos D, Semba S, Fabbri M, Druck T, Volinia S, et al. A role for the WWOX gene in prostate cancer. Cancer Res. 2006;66:6477-81 pubmed
    Expression of the WWOX gene, encompassing the common chromosome fragile site FRA16D, is altered in a large fraction of cancers of various types, including prostate cancer...
  55. Kosla K, Pluciennik E, Kurzyk A, Jesionek Kupnicka D, Kordek R, Potemski P, et al. Molecular analysis of WWOX expression correlation with proliferation and apoptosis in glioblastoma multiforme. J Neurooncol. 2011;101:207-13 pubmed publisher
    Glioblastoma multiforme is the most common type of primary brain tumor in adults. WWOX is a tumor suppressor gene involved in carcinogenesis and cancer progression in many different neoplasms...
  56. Ried K, Finnis M, Hobson L, Mangelsdorf M, Dayan S, Nancarrow J, et al. Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells. Hum Mol Genet. 2000;9:1651-63 pubmed
    ..The FRA16D DNA sequence also led to the identification of an alternatively spliced gene, named FOR (fragile site FRA16D oxidoreductase), exons of which span both the fragile site and the minimal region of homozygous deletion...
  57. Del Mare S, Salah Z, Aqeilan R. WWOX: its genomics, partners, and functions. J Cell Biochem. 2009;108:737-45 pubmed publisher
    ..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/..
  58. Vasan R, Glazer N, Felix J, Lieb W, Wild P, Felix S, et al. Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data. JAMA. 2009;302:168-78 pubmed publisher
    ..In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry)...
  59. Guo W, Dong Z, Dong Y, Guo Y, Kuang G, Yang Z. Genetic and epigenetic alterations of WWOX in the development of gastric cardia adenocarcinoma. Environ Mol Mutagen. 2013;54:112-23 pubmed publisher
    WWOX is a tumor suppressor gene that maps to the common fragile site FRA16D and is involved in carcinogenesis and cancer progression in many different carcinomas...
  60. Guo W, Wang G, Dong Y, Guo Y, Kuang G, Dong Z. Decreased expression of WWOX in the development of esophageal squamous cell carcinoma. Mol Carcinog. 2013;52:265-74 pubmed publisher
    ..3-24.1 in the region recognized as the common fragile site FRA16D is considered to be a tumor suppressor gene involved in various carcinomas...
  61. Chen S, Chuang J, Wang J, Tsai M, Li H, Chang N. Expression of WW domain-containing oxidoreductase WOX1 in the developing murine nervous system. Neuroscience. 2004;124:831-9 pubmed
    WW domain-containing oxidoreductase WOX1, also known as WWOX or FOR, is a proapoptotic protein and a putative tumor suppressor...
  62. Aqeilan R, Kuroki T, Pekarsky Y, Albagha O, Trapasso F, Baffa R, et al. Loss of WWOX expression in gastric carcinoma. Clin Cancer Res. 2004;10:3053-8 pubmed
    WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene that maps to the common fragile site FRA16D on chromosome 16q23.3-24.1...
  63. Chang N, Doherty J, Ensign A, Schultz L, Hsu L, Hong Q. WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53. J Biol Chem. 2005;280:43100-8 pubmed
    WW domain-containing oxidoreductase WOX1, also named WWOX or FOR, undergoes Tyr33 phosphorylation at its first N-terminal WW domain and subsequent nuclear translocation in response to sex steroid hormones and stress stimuli...
  64. Jenner M, Leone P, Walker B, Ross F, Johnson D, Gonzalez D, et al. Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma. Blood. 2007;110:3291-300 pubmed
    ..location of CYLD), and a region centered on 16q23 (the location of the WW domain-containing oxidoreductase gene WWOX)...
  65. Zhang P, Jia R, Ying L, Liu B, Qian G, Fan X, et al. WWOX-mediated apoptosis in A549 cells mainly involves the mitochondrial pathway. Mol Med Rep. 2012;6:121-4 pubmed publisher
    ..3-24.1, a chromosome region that spans the common fragile site, FRA16D. Abnormal transcripts or even loss of expression are frequently found in a number of ..
  66. Nunez M, Ludes Meyers J, Aldaz C. WWOX protein expression in normal human tissues. J Mol Histol. 2006;37:115-25 pubmed
    ..spans approximately a 1 Mb genomic region and is the site for the second most common chromosomal fragile site, FRA16D at 16q23...
  67. Płuciennik E, Nowakowska M, Wujcicka W, Sitkiewicz A, Kazanowska B, Zielinska E, et al. Genetic alterations of WWOX in Wilms' tumor are involved in its carcinogenesis. Oncol Rep. 2012;28:1417-22 pubmed publisher
    ..Within this region, known as common fragile site FRA16D, the WWOX tumor suppressor gene is located...
  68. Chiang M, Yeh S, Liao H, Chang N, Chen Y. Overexpression of WW domain-containing oxidoreductase WOX1 preferentially induces apoptosis in human glioblastoma cells harboring mutant p53. Biomed Pharmacother. 2012;66:433-8 pubmed publisher
    Human WWOX gene encoding WW domain-containing oxidoreductase, named WWOX, FOR, or WOX1, has been studied in various types of cancer cells and shown to be a tumor suppressor with pro-apoptotic properties...
  69. Ekizoglu S, Muslumanoglu M, Dalay N, Buyru N. Genetic alterations of the WWOX gene in breast cancer. Med Oncol. 2012;29:1529-35 pubmed publisher
    FRA3B and FRA16D are the most sensitive common chromosomal fragile site loci in the human genome and two tumor suppressor genes FHIT (Fragile Histidine Triad) and WWOX (WW domain-containing oxidoreductase gene) map to this sites...
  70. Feng S, Muraoka Cook R, Hunter D, Sandahl M, Caskey L, Miyazawa K, et al. The E3 ubiquitin ligase WWP1 selectively targets HER4 and its proteolytically derived signaling isoforms for degradation. Mol Cell Biol. 2009;29:892-906 pubmed publisher
    ..Here we report that s80(HER4) Cyt1 action increased the expression of WWP1 (for WW domain-containing protein 1), an E3 ubiquitin ligase, but not other members of the Nedd4 E3 ligase family...
  71. Göthlin Eremo A, Wegman P, Stal O, Nordenskjold B, Fornander T, Wingren S. Wwox expression may predict benefit from adjuvant tamoxifen in randomized breast cancer patients. Oncol Rep. 2013;29:1467-74 pubmed publisher
    Reduced or absent Wwox expression has recently been associated with tamoxifen resistance in breast cancer and has also been proposed as a candidate predictive marker for treatment...
  72. Nunez M, Rosen D, Ludes Meyers J, Abba M, Kil H, Page R, et al. WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome. BMC Cancer. 2005;5:64 pubmed
    The putative tumor suppressor WWOX gene spans the common chromosomal fragile site 16D (FRA16D) at chromosome area 16q23.3-24.1...
  73. Zhang J, Li L, Song H, Paige A, Gabra H. [Effect of WWOX gene on the attachment and adhesion of ovarian cancer cells]. Zhonghua Fu Chan Ke Za Zhi. 2009;44:529-32 pubmed
    To explore the relationship between WWOX gene and attachment and adhesion of ovarian cancer...
  74. Iliopoulos D, Fabbri M, Druck T, Qin H, Han S, Huebner K. Inhibition of breast cancer cell growth in vitro and in vivo: effect of restoration of Wwox expression. Clin Cancer Res. 2007;13:268-74 pubmed
    The WWOX gene is down-regulated in breast cancer and loss of Wwox expression correlates with important clinical features of breast cancer. Thus, we have examined the effect of restoration of Wwox expression in breast cancer-derived cells...