系統識別號 U0026-2808201217525300
論文名稱(中文) 鋅手指樣蛋白對特定癌症誘發免疫反應以達抗癌效果
論文名稱(英文) Self-polymerizing Zfra peptides elicit immune response for targeting cancer
校院名稱 成功大學
系所名稱(中) 分子醫學研究所
系所名稱(英) Institute of Molecular Medicine
學年度 100
學期 2
出版年 101
研究生(中文) 蘇婉佩
研究生(英文) Wan-Pei Su
學號 T16981041
學位類別 碩士
語文別 英文
論文頁數 63頁
口試委員 指導教授-張南山
中文關鍵字 鋅手指樣蛋白  含雙色胺酸功能區氧化還原酶  玻尿酸酶-2  細胞凋亡  抗癌胜肽  神經膠質瘤  乳癌  神經母細胞瘤  皮膚癌 
英文關鍵字 Zfra  WOX1  Hyal-2  apoptosis  anti-cancer peptide  glioma  neuroblastoma  breast cancer  skin cancer 
中文摘要 Zfra(Zinc finger-like protein that regulates apoptosis) 參與在TNF訊息傳導路徑中,並且與腫瘤抑制蛋白WOX1有交互作用。Zfra可於活體外模式下引起細胞凋亡,當Zfra的Ser8改變成Gly時則會破壞這項能力。最近我們證實了,部分蛋白質一旦與Zfra共價結合,被Zfra化(Zfration)的蛋白質將會透過非泛素/蛋白酶體(proteasome/ubiquitination)的路徑快速降解。Zfra可抑制WOX1引起的細胞凋亡,但Zfra影響WOX1的機制尚不清楚,在此,我們證實了Zfra與WOX1間可能是透過共價鍵鍵結,此外也證實了Zfra中的Ser6和Ser7未參與在調控Zfra所引起的細胞凋亡中。在活體實驗中,預先於裸鼠尾靜脈注射Zfra1-31或截斷型的Zfra4-10可抑制人類神經膠質瘤U87-MG,乳癌細胞MDA-MB-468,神經母細胞瘤SH-SY5Y以及皮膚癌細胞的生長。將施打過Zfra的裸鼠的脾臟細胞注射到NOD SCID老鼠血液中,這些NOD SCID對於植入的腫瘤也具有抗性,推測存在有一群非T細胞的免疫細胞參與在限制腫瘤生長中。在Zfra注射前,預先注射辨認B或T細胞的抗體,我們發現CD19+、CD27+或IL2R-α+的細胞可能為Zfra作用的標的細胞或者是參與在調控Zfra於活體內預防癌症的能力。此外,我們也發現了一個具有成為Zfra受器的蛋白,Hyal-2 (Hyaluronidase type 2),Hyal-2抗體可於裸鼠、NOD-SCID以及BALB/c中抑制皮膚癌生的生長。我們的結果推測Zfra可能是透過活化Hyal-2+的免疫細胞以達到抗癌效果。
英文摘要 Zfra (Zinc finger-like protein that regulates apoptosis), which is involved in TNF signaling, physically interacts with a candidate tumor suppressor WOX1. Zfra induces cancer cell apoptosis in vitro, while alteration Ser8 in Zfra to Gly would abolishes the apoptotic effects. Most recently, we demonstrated that once covalently interacted with Zfra (zfration), the zfrated proteins undergo rapid degradation through the proteasome/ubiquitination-indepen- dent pathway. Zfra abolishes the apoptosis induced by WOX1. How Zfra affects the WOX1 apoptotic functions is not clear. Here, we demonstrated that Zfra may covalently bind to WOX1. On the other hand, Ser6 and Ser7 are not involved in Zfra-mediated cell death. Pre-injection of the full length Zfral-31, or truncated Zfra4-10, via tail vein protects nude mice from growing human glioma U87-MG, breast cancer MDA-MB-468, neuroblastoma SH-SY5Y and skin cancers. When spleen cells from Zfra-treated nude mice were transferred to NOD SCID mice, these mice became resistant to the growth of implanted cancer cells, suggesting that non-T “memory” cells are involved in blocking cancer growth. Pre-treating nude mice with antibodies which against B or T-cells before Zfra stimulation, we found CD19+, CD27+ or IL2R-α+ cells may be the Zfra target cells or participating in regulate Zfra prevention in vivo. Furthermore, we found a potential Zfra receptor, Hyal-2 (Hyaluronidase type 2). Hyal-2 antiserum inhibits skin cancer growth in nude mice, NOD SCID and BAB/c. Our results suggest that Zfra may activate Hyal-2+ immune cells for targeting cancer.
論文目次 中文摘要 I
Abstract II
誌謝 III
Table of contents IV
Index of figures VI
Abbreviation VII
Introduction 1
Goals of This Study 1
Zinc Finger-like Protein that Regulates Apoptosis, Zfra 2
WW Domain-Containing Oxidoreductase 6
Hyaluronic Acid (Hyaluronan, HA) 12
Materials and Methods 18
Cell Lines 18
cDNA Constructs and Transient Gene Expression 18
Site-Directed Mutagenesis 19
Cell Cycle Analysis 19
Co-immunoprecipitation, Immunoblotting with Antibodies 20
Zfra Peptide Preparation, Antibodies, and Tumor Xenografts 21
Statistical Analysis 22
Results 23
Zfra may Covalently Bind WOX1 23
Ser6 and Ser7 Are Not Involved in Zfra-Mediated Cell Death 23
Zfra Suppresses the Growth of Glioma U87-MG, Neuroblastoma, and Breast Cancer 24
Zfra Primes Spleen Cells for Cancer Suppression 24
Zfra Suppresses Melanoma B16F10 Metastasis 25
Zfra Inhibits Cancer Cells Growth through Activating a Novel Population of Spleen Cells 26
Hyal-2 Is a Potential Receptor of Zfra 27
Hyal-2+ cell Are Responsible for Preventing Cancer Growth 27
Ultrasonicated Hyaluronan But Not Wild Type Prevent Melanoma Cell Growth In Vivo 28
Discussion 30
Self-polymerization and Anti-cancer Function of Zfra 30
Zfra in Cancer Prevention 31
Zfra Activates Novel Spleen Cells for Targeting cancer 31
Hyal-2+ Cells in Cancer Prevention 32
Activation of Hyal-2+ Cells 33
References 34
Figures 48
參考文獻 Abdeen SK, Salah Z, Maly B, Smith Y, Tufail R, Abu-Odeh M, Zanesi N, Croce CM, Nawaz Z, Aqeilan RI (2011) Wwox inactivation enhances mammary tumorigenesis. Oncogene 30: 3900-3906

Aqeilan RI, Hagan JP, Aqeilan HA, Pichiorri F, Fong LY, Croce CM (2007) Inactivation of the Wwox gene accelerates forestomach tumor progression in vivo. Cancer Res 67: 5606-5610

Aqeilan RI, Hagan JP, de Bruin A, Rawahneh M, Salah Z, Gaudio E, Siddiqui H, Volinia S, Alder H, Lian JB, Stein GS, Croce CM (2009) Targeted ablation of the WW domain-containing oxidoreductase tumor suppressor leads to impaired steroidogenesis. Endocrinology 150: 1530-1535

Aqeilan RI, Hassan MQ, de Bruin A, Hagan JP, Volinia S, Palumbo T, Hussain S, Lee SH, Gaur T, Stein GS, Lian JB, Croce CM (2008) The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism. J Biol Chem 283: 21629-21639

Aqeilan RI, Palamarchuk A, Weigel RJ, Herrero JJ, Pekarsky Y, Croce CM (2004a) Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2gamma transcription factor. Cancer Res 64: 8256-8261

Aqeilan RI, Pekarsky Y, Herrero JJ, Palamarchuk A, Letofsky J, Druck T, Trapasso F, Han SY, Melino G, Huebner K, Croce CM (2004b) Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proc Natl Acad Sci U S A 101: 4401-4406

Bai KJ, Spicer AP, Mascarenhas MM, Yu L, Ochoa CD, Garg HG, Quinn DA (2005) The role of hyaluronan synthase 3 in ventilator-induced lung injury. Am J Respir Crit Care Med 172: 92-98

Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG (1999) LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol 144: 789-801

Baykara O, Demirkaya A, Kaynak K, Tanju S, Toker A, Buyru N (2010) WWOX gene may contribute to progression of non-small-cell lung cancer (NSCLC). Tumour Biol 31: 315-320

Becker S, Markova B, Wiewrodt R, Hoffarth S, Hahnel PS, Pleiner S, Schmidt LH, Breitenbuecher F, Schuler M (2011) Functional and clinical characterization of the putative tumor suppressor WWOX in non-small cell lung cancer. J Thorac Oncol 6: 1976-1983

Beech DJ, Madan AK, Deng N (2002) Expression of PH-20 in normal and neoplastic breast tissue. J Surg Res 103: 203-207

Bertrand P, Girard N, Delpech B, Duval C, d'Anjou J, Dauce JP (1992) Hyaluronan (hyaluronic acid) and hyaluronectin in the extracellular matrix of human breast carcinomas: comparison between invasive and non-invasive areas. Int J Cancer 52: 1-6

Camenisch TD, Spicer AP, Brehm-Gibson T, Biesterfeldt J, Augustine ML, Calabro A, Jr., Kubalak S, Klewer SE, McDonald JA (2000) Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme. J Clin Invest 106: 349-360

Cantor JP, Iliopoulos D, Rao AS, Druck T, Semba S, Han SY, McCorkell KA, Lakshman TV, Collins JE, Wachsberger P, Friedberg JS, Huebner K (2007) Epigenetic modulation of endogenous tumor suppressor expression in lung cancer xenografts suppresses tumorigenicity. Int J Cancer 120: 24-31

Cao H, Mattison J, Zhao Y, Joki N, Grasso M, Chang NS (1996) Regulation of tumor necrosis factor-and Fas-mediated apoptotic cell death by a novel cDNA TR2L. Biochem Biophys Res Commun 227: 266-272

Casadei R, Piovesan A, Vitale L, Facchin F, Pelleri MC, Canaider S, Bianconi E, Frabetti F, Strippoli P (2012) Genome-scale analysis of human mRNA 5' coding sequences based on expressed sequence tag (EST) database. Genomics 100: 125-130

Chang JY, He RY, Lin HP, Hsu LJ, Lai FJ, Hong Q, Chen SJ, Chang NS (2010) Signaling from membrane receptors to tumor suppressor WW domain-containing oxidoreductase. Exp Biol Med (Maywood) 235: 796-804

Chang NS (1997) Hyaluronidase enhancement of TNF-mediated cell death is reversed by TGF-beta 1. Am J Physiol 273: C1987-1994

Chang NS (2002) A potential role of p53 and WOX1 in mitochondrial apoptosis (review). Int J Mol Med 9: 19-24

Chang NS, Doherty J, Ensign A (2003a) JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis. J Biol Chem 278: 9195-9202

Chang NS, Doherty J, Ensign A, Lewis J, Heath J, Schultz L, Chen ST, Oppermann U (2003b) Molecular mechanisms underlying WOX1 activation during apoptotic and stress responses. Biochem Pharmacol 66: 1347-1354

Chang NS, Hsu LJ, Lin YS, Lai FJ, Sheu HM (2007) WW domain-containing oxidoreductase: a candidate tumor suppressor. Trends Mol Med 13: 12-22

Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, Zevotek N (2001) Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity. J Biol Chem 276: 3361-3370

Chang NS, Schultz L, Hsu LJ, Lewis J, Su M, Sze CI (2005) 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 24: 714-723

Chen ST, Chuang JI, Wang JP, Tsai MS, Li H, Chang NS (2004) Expression of WW domain-containing oxidoreductase WOX1 in the developing murine nervous system. Neuroscience 124: 831-839

Choi J, Kim CH, Kim D, Chung SJ, Song JH, Kang JM, Yang JI, Park MJ, Kim YS, Yim JY, Lim SH, Kim JS, Jung HC, Song IS (2011) Prospective evaluation of a new stool antigen test for the detection of Helicobacter pylori, in comparison with histology, rapid urease test, (13)C-urea breath test, and serology. J Gastroenterol Hepatol 26: 1053-1059

Csoka AB, Frost GI, Stern R (2001) The six hyaluronidase-like genes in the human and mouse genomes. Matrix Biol 20: 499-508

Day AJ, Sheehan JK (2001) Hyaluronan: polysaccharide chaos to protein organisation. Curr Opin Struct Biol 11: 617-622

Del Mare S, Kurek KC, Stein GS, Lian JB, Aqeilan RI (2011) Role of the WWOX tumor suppressor gene in bone homeostasis and the pathogenesis of osteosarcoma. Am J Cancer Res 1: 585-594

Dias EP, Pimenta FJ, Sarquis MS, Dias Filho MA, Aldaz CM, Fujii JB, Gomez RS, De Marco L (2007) Association between decreased WWOX protein expression and thyroid cancer development. Thyroid : official journal of the American Thyroid Association 17: 1055-1059

Donati V, Fontanini G, Dell'Omodarme M, Prati MC, Nuti S, Lucchi M, Mussi A, Fabbri M, Basolo F, Croce CM, Aqeilan RI (2007) WWOX expression in different histologic types and subtypes of non-small cell lung cancer. Clin Cancer Res 13: 884-891

Dudekula S, Lee MH, Hsu LJ, Chen SJ, Chang NS (2010) Zfra is a small wizard in the mitochondrial apoptosis. Aging (Albany NY) 2: 1023-1029

Elkin M, Vlodavsky I (2001) Tail vein assay of cancer metastasis. Curr Protoc Cell Biol Chapter 19: Unit 19 12

Esashi E, Ito H, Ishihara K, Hirano T, Koyasu S, Miyajima A (2004) Development of CD4+ macrophages from intrathymic T cell progenitors is induced by thymic epithelial cells. J Immunol 173: 4360-4367

Evanko SP, Johnson PY, Braun KR, Underhill CB, Dudhia J, Wight TN (2001) Platelet-derived growth factor stimulates the formation of versican-hyaluronan aggregates and pericellular matrix expansion in arterial smooth muscle cells. Arch Biochem Biophys 394: 29-38

Frost GI, Csoka AB, Wong T, Stern R (1997) Purification, cloning, and expression of human plasma hyaluronidase. Biochem Biophys Res Commun 236: 10-15

Girish KS, Kemparaju K (2007) The magic glue hyaluronan and its eraser hyaluronidase: a biological overview. Life Sci 80: 1921-1943

Godin DA, Fitzpatrick PC, Scandurro AB, Belafsky PC, Woodworth BA, Amedee RG, Beech DJ, Beckman BS (2000) PH20: a novel tumor marker for laryngeal cancer. Arch Otolaryngol Head Neck Surg 126: 402-404

Gritsenko PG, Ilina O, Friedl P (2012) Interstitial guidance of cancer invasion. J Pathol 226: 185-199

Guler G, Uner A, Guler N, Han SY, Iliopoulos D, McCue P, Huebner K (2005) Concordant loss of fragile gene expression early in breast cancer development. Pathology international 55: 471-478

Gust KM, Hofer MD, Perner SR, Kim R, Chinnaiyan AM, Varambally S, Moller P, Rinnab L, Rubin MA, Greiner J, Schmitt M, Kuefer R, Ringhoffer M (2009) RHAMM (CD168) is overexpressed at the protein level and may constitute an immunogenic antigen in advanced prostate cancer disease. Neoplasia 11: 956-963

Hair PS, Gronemus JQ, Crawford KB, Salvi VP, Cunnion KM, Thielens NM, Arlaud GJ, Rawal N, Krishna NK (2010) Human astrovirus coat protein binds C1q and MBL and inhibits the classical and lectin pathways of complement activation. Mol Immunol 47: 792-798

Harada H, Takahashi M (2007) CD44-dependent intracellular and extracellular catabolism of hyaluronic acid by hyaluronidase-1 and -2. J Biol Chem 282: 5597-5607

Hemming R, Martin DC, Slominski E, Nagy JI, Halayko AJ, Pind S, Triggs-Raine B (2008) Mouse Hyal3 encodes a 45- to 56-kDa glycoprotein whose overexpression increases hyaluronidase 1 activity in cultured cells. Glycobiology 18: 280-289

Hong Q, Hsu LJ, Schultz L, Pratt N, Mattison J, Chang NS (2007) Zfra affects TNF-mediated cell death by interacting with death domain protein TRADD and negatively regulates the activation of NF-kappaB, JNK1, p53 and WOX1 during stress response. BMC Mol Biol 8: 50

Hong Q, Sze CI, Lin SR, Lee MH, He RY, Schultz L, Chang JY, Chen SJ, Boackle RJ, Hsu LJ, Chang NS (2009) Complement C1q activates tumor suppressor WWOX to induce apoptosis in prostate cancer cells. PLoS One 4: e5755

Hsu LJ, Hong Q, Schultz L, Kuo E, Lin SR, Lee MH, Lin YS, Chang NS (2008) Zfra is an inhibitor of Bcl-2 expression and cytochrome c release from the mitochondria. Cell Signal 20: 1303-1312

Hsu LJ, Schultz L, Hong Q, Van Moer K, Heath J, Li MY, Lai FJ, Lin SR, Lee MH, Lo CP, Lin YS, Chen ST, Chang NS (2009) Transforming growth factor beta1 signaling via interaction with cell surface Hyal-2 and recruitment of WWOX/WOX1. J Biol Chem 284: 16049-16059

Hsu LJ, Schultz L, Mattison J, Lin YS, Chang NS (2005) Cloning and characterization of a small-size peptide Zfra that regulates the cytotoxic function of tumor necrosis factor by interacting with JNK1. Biochem Biophys Res Commun 327: 415-423

Hull RL, Johnson PY, Braun KR, Day AJ, Wight TN (2012) Hyaluronan and Hyaluronan Binding Proteins Are Normal Components of Mouse Pancreatic Islets and Are Differentially Expressed by Islet Endocrine Cell Types. J Histochem Cytochem

Iliopoulos D, Fabbri M, Druck T, Qin HR, Han SY, Huebner K (2007) Inhibition of breast cancer cell growth in vitro and in vivo: effect of restoration of Wwox expression. Clin Cancer Res 13: 268-274

Inoue I, Mukoubayashi C, Yoshimura N, Niwa T, Deguchi H, Watanabe M, Enomoto S, Maekita T, Ueda K, Iguchi M, Yanaoka K, Tamai H, Arii K, Oka M, Fujishiro M, Takeshita T, Iwane M, Mohara O, Ichinose M (2011) Elevated risk of colorectal adenoma with Helicobacter pylori-related chronic gastritis: a population-based case-control study. Int J Cancer 129: 2704-2711

Itano N, Kimata K (2002) Mammalian hyaluronan synthases. IUBMB Life 54: 195-199

Itano N, Sawai T, Atsumi F, Miyaishi O, Taniguchi S, Kannagi R, Hamaguchi M, Kimata K (2004) Selective expression and functional characteristics of three mammalian hyaluronan synthases in oncogenic malignant transformation. J Biol Chem 279: 18679-18687

J. Necas LB, P. Brauner, J. Kolar (2008) Hyaluronic acid (hyaluronan): a review. Veterinarni Medicina 8: 397–411

Jacobson A, Brinck J, Briskin MJ, Spicer AP, Heldin P (2000) Expression of human hyaluronan synthases in response to external stimuli. Biochem J 348 Pt 1: 29-35

Jin C, Ge L, Ding X, Chen Y, Zhu H, Ward T, Wu F, Cao X, Wang Q, Yao X (2006) PKA-mediated protein phosphorylation regulates ezrin-WWOX interaction. Biochem Biophys Res Commun 341: 784-791

Josefsson A, Adamo H, Hammarsten P, Granfors T, Stattin P, Egevad L, Laurent AE, Wikstrom P, Bergh A (2011) Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome. Am J Pathol 179: 1961-1968

Klug A (2010) The discovery of zinc fingers and their applications in gene regulation and genome manipulation. Annual review of biochemistry 79: 213-231

Kosla K, Pluciennik E, Kurzyk A, Jesionek-Kupnicka D, Kordek R, Potemski P, Bednarek AK (2011) Molecular analysis of WWOX expression correlation with proliferation and apoptosis in glioblastoma multiforme. J Neurooncol 101: 207-213

Kurek KC, Del Mare S, Salah Z, Abdeen S, Sadiq H, Lee SH, Gaudio E, Zanesi N, Jones KB, DeYoung B, Amir G, Gebhardt M, Warman M, Stein GS, Stein JL, Lian JB, Aqeilan RI (2010) Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression. Cancer Res 70: 5577-5586

Lai FJ, Cheng CL, Chen ST, Wu CH, Hsu LJ, Lee JY, Chao SC, Sheen MC, Shen CL, Chang NS, Sheu HM (2005) 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 11: 5769-5777

Lawson C, Wolf S (2009) ICAM-1 signaling in endothelial cells. Pharmacol Rep 61: 22-32

Lee JY, Spicer AP (2000) Hyaluronan: a multifunctional, megaDalton, stealth molecule. Curr Opin Cell Biol 12: 581-586

Li MY, Lai FJ, Hsu LJ, Lo CP, Cheng CL, Lin SR, Lee MH, Chang JY, Subhan D, Tsai MS, Sze CI, Pugazhenthi S, Chang NS, Chen ST (2009) Dramatic co-activation of WWOX/WOX1 with CREB and NF-kappaB in delayed loss of small dorsal root ganglion neurons upon sciatic nerve transection in rats. PLoS One 4: e7820

Lim YJ, Yang CH (2012) Non-steroidal anti-inflammatory drug-induced enteropathy. Clin Endosc 45: 138-144

Lin HP, Chang JY, Lin SR, Lee MH, Huang SS, Hsu LJ, Chang NS (2011) Identification of an In Vivo MEK/WOX1 Complex as a Master Switch for Apoptosis in T Cell Leukemia. Genes Cancer 2: 550-562

Lin JT, Tzai TS, Liao CY, Wang JS, Wu TT, Wang HY, Wu CH, Yu CC, Lu PJ (2012) WWOX Protein Expression Varies Among RCC Histotypes and Downregulation of WWOX Protein Correlates with Less-Favorable Prognosis in Clear RCC. Annals of surgical oncology

Lo CP, Hsu LJ, Li MY, Hsu SY, Chuang JI, Tsai MS, Lin SR, Chang NS, Chen ST (2008) MPP+-induced neuronal death in rats involves tyrosine 33 phosphorylation of WW domain-containing oxidoreductase WOX1. Eur J Neurosci 27: 1634-1646

Lynn BD, Li X, Cattini PA, Turley EA, Nagy JI (2001) Identification of sequence, protein isoforms, and distribution of the hyaluronan-binding protein RHAMM in adult and developing rat brain. J Comp Neurol 439: 315-330

Ma SH, Liu QJ, Zhang YC, Yang R (2011) Alternative surgical strategies in patients with sporadic medullary thyroid carcinoma: Long-term follow-up. Oncol Lett 2: 975-980

Mahajan NP, Whang YE, Mohler JL, Earp HS (2005) Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer Res 65: 10514-10523

McDonald CB, Buffa L, Bar-Mag T, Salah Z, Bhat V, Mikles DC, Deegan BJ, Seldeen KL, Malhotra A, Sudol M, Aqeilan RI, Nawaz Z, Farooq A (2012) Biophysical Basis of the Binding of WWOX Tumor Suppressor to WBP1 and WBP2 Adaptors. J Mol Biol

Nunez MI, Ludes-Meyers J, Abba MC, Kil H, Abbey NW, Page RE, Sahin A, Klein-Szanto AJ, Aldaz CM (2005a) Frequent loss of WWOX expression in breast cancer: correlation with estrogen receptor status. Breast Cancer Res Treat 89: 99-105

Nunez MI, Ludes-Meyers J, Aldaz CM (2006) WWOX protein expression in normal human tissues. J Mol Histol 37: 115-125

Nunez MI, Rosen DG, Ludes-Meyers JH, Abba MC, Kil H, Page R, Klein-Szanto AJ, Godwin AK, Liu J, Mills GB, Aldaz CM (2005b) WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome. BMC Cancer 5: 64

Oguchi T, Ishiguro N (2004) Differential stimulation of three forms of hyaluronan synthase by TGF-beta, IL-1beta, and TNF-alpha. Connect Tissue Res 45: 197-205

Pichi F, Morara M, Veronese C, Lembo A, Vitale L, Ciardella AP, Nucci P (2012) Double-vitrectomy for optic disc pit maculopathy. Case Report Ophthalmol 3: 156-161

Pienimaki JP, Rilla K, Fulop C, Sironen RK, Karvinen S, Pasonen S, Lammi MJ, Tammi R, Hascall VC, Tammi MI (2001) Epidermal growth factor activates hyaluronan synthase 2 in epidermal keratinocytes and increases pericellular and intracellular hyaluronan. J Biol Chem 276: 20428-20435

Pluciennik E, Kusinska R, Potemski P, Kubiak R, Kordek R, Bednarek AK (2006) WWOX--the FRA16D cancer gene: expression correlation with breast cancer progression and prognosis. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 32: 153-157

Qin HR, Iliopoulos D, Semba S, Fabbri M, Druck T, Volinia S, Croce CM, Morrison CD, Klein RD, Huebner K (2006) A role for the WWOX gene in prostate cancer. Cancer Res 66: 6477-6481

Reese KL, Aravindan RG, Griffiths GS, Shao M, Wang Y, Galileo DS, Atmuri V, Triggs-Raine BL, Martin-Deleon PA (2010) Acidic hyaluronidase activity is present in mouse sperm and is reduced in the absence of SPAM1: evidence for a role for hyaluronidase 3 in mouse and human sperm. Mol Reprod Dev 77: 759-772

Sayo T, Sugiyama Y, Takahashi Y, Ozawa N, Sakai S, Ishikawa O, Tamura M, Inoue S (2002) Hyaluronan synthase 3 regulates hyaluronan synthesis in cultured human keratinocytes. J Invest Dermatol 118: 43-48

Scott JE, Cummings C, Brass A, Chen Y (1991) Secondary and tertiary structures of hyaluronan in aqueous solution, investigated by rotary shadowing-electron microscopy and computer simulation. Hyaluronan is a very efficient network-forming polymer. Biochem J 274 ( Pt 3): 699-705

Shimabukuro Y, Terashima H, Takedachi M, Maeda K, Nakamura T, Sawada K, Kobashi M, Awata T, Oohara H, Kawahara T, Iwayama T, Hashikawa T, Yanagita M, Yamada S, Murakami S (2011) Fibroblast growth factor-2 stimulates directed migration of periodontal ligament cells via PI3K/AKT signaling and CD44/hyaluronan interaction. J Cell Physiol 226: 809-821

Simpson MA, Wilson CM, McCarthy JB (2002) Inhibition of prostate tumor cell hyaluronan synthesis impairs subcutaneous growth and vascularization in immunocompromised mice. Am J Pathol 161: 849-857

Spano D, Zollo M (2012) Tumor microenvironment: a main actor in the metastasis process. Clin Exp Metastasis 29: 381-395

Stamenkovic I, Aruffo A, Amiot M, Seed B (1991) The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells. EMBO J 10: 343-348

Stern R (2004) Hyaluronan catabolism: a new metabolic pathway. Eur J Cell Biol 83: 317-325

Sugiyama Y, Shimada A, Sayo T, Sakai S, Inoue S (1998) Putative hyaluronan synthase mRNA are expressed in mouse skin and TGF-beta upregulates their expression in cultured human skin cells. J Invest Dermatol 110: 116-121

Suzuki K, Yamamoto T, Usui T, Heldin P, Yamashita H (2003) Expression of hyaluronan synthase in intraocular proliferative diseases: regulation of expression in human vascular endothelial cells by transforming growth factor-beta. Jpn J Ophthalmol 47: 557-564

Sze CI, Su M, Pugazhenthi S, Jambal P, Hsu LJ, Heath J, Schultz L, Chang NS (2004) Down-regulation of WW domain-containing oxidoreductase induces Tau phosphorylation in vitro. A potential role in Alzheimer's disease. J Biol Chem 279: 30498-30506

Tammi RH, Passi AG, Rilla K, Karousou E, Vigetti D, Makkonen K, Tammi MI (2011) Transcriptional and post-translational regulation of hyaluronan synthesis. FEBS J 278: 1419-1428

Toole BP, Wight TN, Tammi MI (2002) Hyaluronan-cell interactions in cancer and vascular disease. J Biol Chem 277: 4593-4596

Vitale LA, He LZ, Thomas LJ, Widger J, Weidlick J, Crocker A, O'Neill T, Storey J, Glennie MJ, Grote DM, Ansell SM, Marsh H, Keler T (2012) Development of a Human Monoclonal Antibody for Potential Therapy of CD27-Expressing Lymphoma and Leukemia. Clin Cancer Res 18: 3812-3821

Wang F, Grigorieva EV, Li J, Senchenko VN, Pavlova TV, Anedchenko EA, Kudryavtseva AV, Tsimanis A, Angeloni D, Lerman MI, Kashuba VI, Klein G, Zabarovsky ER (2008) HYAL1 and HYAL2 inhibit tumour growth in vivo but not in vitro. PLoS One 3: e3031

Wang HY, Juo LI, Lin YT, Hsiao M, Lin JT, Tsai CH, Tzeng YH, Chuang YC, Chang NS, Yang CN, Lu PJ (2012) WW domain-containing oxidoreductase promotes neuronal differentiation via negative regulation of glycogen synthase kinase 3beta. Cell Death Differ 19: 1049-1059

Wang X, Chao L, Jin G, Ma G, Zang Y, Sun J (2009) Association between CpG island methylation of the WWOX gene and its expression in breast cancers. Tumour Biol 30: 8-14

Watanabe A, Hippo Y, Taniguchi H, Iwanari H, Yashiro M, Hirakawa K, Kodama T, Aburatani H (2003) An opposing view on WWOX protein function as a tumor suppressor. Cancer Res 63: 8629-8633

Weigand S, Herting F, Maisel D, Nopora A, Voss E, Schaab C, Klammer M, Tebbe A (2012) Global quantitative phosphoproteome analysis of human tumor xenografts treated with a CD44 antagonist. Cancer Res

Winkel K, Sotzik F, Vremec D, Cameron PU, Shortman K (1994) CD4 and CD8 expression by human and mouse thymic dendritic cells. Immunol Lett 40: 93-99

Won-Pei Su S-HC, Szu-Jung Chen,Pei-Yi Chou, Chun-Cheng Huang ,Nan-Shan Chang (2012) WW Domain-Containing Oxidoreductase is a Potential Receptor for Sex Steroid Hormones. In Sex Hormones, Dubey RK (ed), 1 edn, pp 333-352. InTech

Woodfield GW, Chen Y, Bair TB, Domann FE, Weigel RJ (2010) Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells. Genes Chromosomes Cancer 49: 948-962

Yan J, Zhang M, Zhang J, Chen X, Zhang X (2011) Helicobacter pylori infection promotes methylation of WWOX gene in human gastric cancer. Biochem Biophys Res Commun 408: 99-102

Yang JC, Wang HL, Chern HD, Shun CT, Lin BR, Lin CJ, Wang TH (2011) Role of omeprazole dosage and cytochrome P450 2C19 genotype in patients receiving omeprazole-amoxicillin dual therapy for Helicobacter pylori eradication. Pharmacotherapy 31: 227-238

Yang M, Soga T, Pollard PJ, Adam J (2012a) The emerging role of fumarate as an oncometabolite. Front Oncol 2: 85

Yang W, Cui S, Ma J, Lu Q, Kong C, Liu T, Sun Z (2012b) Cigarette smoking extract causes hypermethylation and inactivation of WWOX gene in T-24 human bladder cancer cells. Neoplasma 59: 216-223

Yeh YC, Chang WL, Yang HB, Cheng HC, Wu JJ, Sheu BS (2011) H. pylori cagL amino acid sequence polymorphism Y58E59 induces a corpus shift of gastric integrin alpha5beta1 related with gastric carcinogenesis. Mol Carcinog 50: 751-759

Zelazowski MJ, Pluciennik E, Pasz-Walczak G, Potemski P, Kordek R, Bednarek AK (2011) WWOX expression in colorectal cancer--a real-time quantitative RT-PCR study. Tumour Biol 32: 551-560

Zhang S, He H, Day AJ, Tseng SC (2012) Constitutive expression of inter-alpha-inhibitor (IalphaI) family proteins and tumor necrosis factor-stimulated gene-6 (TSG-6) by human amniotic membrane epithelial and stromal cells supporting formation of the heavy chain-hyaluronan (HC-HA) complex. J Biol Chem 287: 12433-12444

Zhou B, Weigel JA, Fauss L, Weigel PH (2000) Identification of the hyaluronan receptor for endocytosis (HARE). J Biol Chem 275: 37733-37741

Zou D, He J, Ma X, Liu W, Chen J, Shi X, Ye P, Gong Y, Zhao Y, Wang R, Yan X, Man X, Gao L, Dent J, Sung J, Wernersson B, Johansson S, Li Z (2011) Helicobacter pylori infection and gastritis: the Systematic Investigation of gastrointestinaL diseases in China (SILC). J Gastroenterol Hepatol 26: 908-915
  • 同意授權校內瀏覽/列印電子全文服務,於2017-08-31起公開。

  • 如您有疑問,請聯絡圖書館