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研究生:呂易謙
研究生(外文):Yi-Chien Lu
論文名稱:鈣網蛋白下游調控因子-岩藻糖轉移酵素調控膀胱癌轉移機制之研究
論文名稱(外文):Fucosyltransferase-1 as a Downstream Effector of Calreticulin in Regulating the metastatic Behavior of Bladder Cancer Cells
指導教授:李心予李心予引用關係
口試委員:張正琪陳炯年許文明朱家瑩
口試日期:2014-06-11
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:生命科學系
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:英文
論文頁數:117
中文關鍵詞:膀胱癌細胞貼附癌症轉移鈣網蛋白岩藻糖轉移酵素整合蛋白活性
外文關鍵詞:Bladder cancerCell adhesionMetastasisCalreticulinFucosyltransferaseβ1-integrin activation
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膀胱癌是國人相當常見之腫瘤,鈣網酪蛋白calreticulin為一多功能蛋白並參與細胞內多種機制,臨床上calreticulin已被使用來檢測膀胱癌。於本研究中,我們成功構築表達低量鈣網酪蛋白之穩定膀胱癌細胞株(J82 CRT-RNAi)顯示降低鈣網酪蛋白之表達會抑制膀胱癌細胞株之移行,並對細胞附著於基質之能力有重要之影響;反之,表達大量鈣網酪蛋白會促進膀胱癌細胞之移行與貼覆基質之能力。更重要的是,降低鈣網酪蛋白之表達亦會抑制膀胱癌細胞株於裸鼠中形成腫瘤,並明顯降低肺臟及肝臟之轉移,這些結果證明了鈣網酪蛋白可能是影響膀胱癌細胞癌化之重要調控因子。藉由核酸晶片比較J82 CRT-RNAi 細胞株與未轉染之細胞間基因表達之差異後,我們發現岩藻醣轉移酵素FUT-1 為其中表達差異性極大的一種蛋白質。岩藻醣化作用為細胞常見之蛋白質修飾,報告指出許多病症與高度岩藻醣化極具相關性。FUT-1 為細胞內負責蛋白質醣基修飾的重要酵素,本研究結果顯示CRT透過調控整合蛋白β1-integrin由FUT1所修飾之岩藻醣化作用,進而影響細胞附著能力。透過大量表達岩藻醣轉移酵素可增加細胞整合蛋白β1-integrin之岩藻醣化程度並有效提升膀胱癌細胞貼附能力。 我們的研究結果更進一步證實,整合蛋白β1-integrin之岩藻醣化作用影響細胞貼附能力是經由調控其整合蛋白本身之活性。 此外,我們也進一步釐清J82 CRT-RNAi 細胞株之FUT-1 表達降低之原因,是由於FUT1 RNA 穩定性下降之結果。根據本研究成果之驗證CRT透過穩定FUT1 mRNA,進而提升β1-integrin岩藻醣化作用藉此促進其活性,影響膀胱癌細胞轉移之能力。

Bladder cancer is a common urothelial cancer. Through proteomic approaches, calreticulin (CRT) was identified and proposed as a urinary marker for bladder cancer. CRT is a multifunctional molecular chaperone that regulates various cellular functions such as Ca2+ homeostasis and cell adhesion. CRT was reported to be overexpressed in various cancers; however, the mechanisms of CRT in bladder tumor development remain unclear. To clarify the roles of CRT in bladder cancer, J82 bladder cancer cells stably overexpressed or knockdown of CRT were generated to investigate the physiological effects of CRT on bladder tumors. Compared to the transfected control vector cells, the knockdown of CRT suppressed cell proliferation, migration, and attachment; on the contrary, overexpression of CRT enhanced cell migration and attachment. Most importantly, we observed that tumors derived from J82 CRT-RNAi cells were significantly smaller and had fewer metastatic sites in the lung and liver in vivo than did transfected control vector cells. To further investigate the precise mechanism of tumor metastasis regulated by CRT, we used DNA array to identify fucosyltransferase-1 (FUT1) as a gene regulated by CRT expression levels. CRT regulated cell adhesion through α1,2-linked fucosylation on β1-integrin and this modification was catalyzed by FUT1. To clarify FUT1 roles in bladder cancer, we transfected the human FUT1 gene into CRT-RNAi stable cell lines. FUT1 overexpression in CRT-RNAi cells resulted in increased levels of β1-integrin fucosylation and rescued cell adhesion to type-I collagen. Treatment with Ulex europaeus agglutinin I (UEA-1), a lectin recognizes FUT1-modified glycosylation structures, did not affect cell adhesion. In contrast, a FUT1-specific fucosidase diminished the activation of β1-integrin. These results indicated that α1,2-fucosylation on β1-integrin were not involved in the integrin-collagen interaction but promoted β1-integrin activation. In addition, we demonstrated that CRT regulated FUT1 mRNA degradation in 3′-untranslated region (3′-UTR). In conclusion, our findings suggested that CRT stabilized FUT1 mRNA, thereby leading to increase in fucosylation of β1-integrin. Furthermore, increased fucosylation levels activate β1-integrin rather than directly modifying the integrin binding sites.

口試委員審定書
致謝………………………………………………………………………………….…i
中文摘要………………………………………………………………………………ii
Abstract……………………………………………………………..………………..iv
List of Tables………………………………………………...………………...……viii
List of Figures………………………………………………..………………………ix
Chapter I. Introduction………………………………………………………………1
1. Fundamental information of calreticulin……………………………………….2
1.1 Protein structure…………………………………………………………………...2
1.2 Location of calreticulin……………………………………………………………3
2. Biological functions of calreticulin……………………………………………....3
2.1 Protein chaperone………………………………………………………………….4
2.2 Calcium homeostasis………………………………………………………………4
2.3 Cell adhesion…………………………………………………………………........5
2.4 RNA stability…………………………………………………………………........5
3. Calreticulin in cancer…………………………………………….........................6
3.1 Clinical outcome of calreticulin levels………………………….............................6
3.2 Functions of CRT in the immune system…………………….................................7
3.3 Functions of CRT in cancer cell proliferation………………..................................8
3.4 Functions of CRT in cell migration and adhesion………………............................9
4. Functions of fucosylation in cancer biology………………...............................11
4.1 Fucosylation in cancer…………………………….…………...............................11
4.2 Fucosyltransferase 1…………………………………………...............................11
4.3 Glycan on integrins regulates its functions………………....................................12
5. Bladder cancer…………………………………...…………...............................13
6. Rationale…………………………………...…………........................................14
Chapter II. Materials and Methods…..………………...………….........................15
Chapter III. Results…………………………………...………….............................28
Chapter IV. Discussions……...…………………………...………….......................40
Chapter V. Concluding remarks and future perspectives…………......................50
References…………………………………...………………………........................53
Appendix I: Changes in tumor growth and metastatic capacities of J82 human bladder cancer cells suppressed by down-regulation of calreticulin expression………………………………...………….................................................97
Appendix II: Calreticulin activates β1-integrin through fucosylation modification by fucosyltransferase-1 in J82 human bladder cancer cells…………………….106



1Michalak, M., Corbett, E. F., Mesaeli, N., Nakamura, K. and Opas, M. (1999) Calreticulin: one protein, one gene, many functions. Biochem J. 344, 281-292
2Michalak, M., Robert Parker, J. M. and Opas, M. (2002) Ca2+ signaling and calcium binding chaperones of the endoplasmic reticulum. Cell Calcium. 32, 269-278
3Rojiani, M. V., Finlay, B. B., Gray, V. and Dedhar, S. (1991) Invitro Interaction of a Polypeptide Homologous to Human-Ro/Ss-a-Antigen (Calreticulin) with a Highly Conserved Amino-Acid-Sequence in the Cytoplasmic Domain of Integrin Alpha-Subunits. Biochemistry-Us. 30, 9859-9866
4Burns, K., Duggan, B., Atkinson, E. A., Famulski, K. S., Nemer, M., Bleackley, R. C. and Michalak, M. (1994) Modulation of gene expression by calreticulin binding to the glucocorticoid receptor. Nature. 367, 476-480
5Martin, V., Groenendyk, J., Steiner, S. S., Guo, L., Dabrowska, M., Parker, J. M., Muller-Esterl, W., Opas, M. and Michalak, M. (2006) Identification by mutational analysis of amino acid residues essential in the chaperone function of calreticulin. J Biol Chem. 281, 2338-2346
6Krause, K. H. and Michalak, M. (1997) Calreticulin. Cell. 88, 439-443
7Baksh, S. and Michalak, M. (1991) Expression of Calreticulin in Escherichia-Coli and Identification of Its Ca2+ Binding Domains. Journal of Biological Chemistry. 266, 21458-21465
8Tjoelker, L. W., Seyfried, C. E., Eddy, R. L., Jr., Byers, M. G., Shows, T. B., Calderon, J., Schreiber, R. B. and Gray, P. W. (1994) Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium binding motifs and gene localization to human chromosome 5. Biochemistry-Us. 33, 3229-3236
9Nakamura, K., Zuppini, A., Arnaudeau, S., Lynch, J., Ahsan, I., Krause, R., Papp, S., De Smedt, H., Parys, J. B., Muller-Esterl, W., Lew, D. P., Krause, K. H., Demaurex, N., Opas, M. and Michalak, M. (2001) Functional specialization of calreticulin domains. J Cell Biol. 154, 961-972
10Corbett, E. F., Oikawa, K., Francois, P., Tessier, D. C., Kay, C., Bergeron, J. J., Thomas, D. Y., Krause, K. H. and Michalak, M. (1999) Ca2+ regulation of interactions between endoplasmic reticulum chaperones. J Biol Chem. 274, 6203-6211
11Michalak, M., Milner, R. E., Burns, K. and Opas, M. (1992) Calreticulin. Biochem J. 285 ( Pt 3), 681-692
12White, T. K., Zhu, Q. and Tanzer, M. L. (1995) Cell surface calreticulin is a putative mannoside lectin which triggers mouse melanoma cell spreading. J Biol Chem. 270, 15926-15929
13Coppolino, M. G., Woodside, M. J., Demaurex, N., Grinstein, S., StArnaud, R. and Dedhar, S. (1997) Calreticulin is essential for integrin-mediated calcium signalling and cell adhesion. Nature. 386, 843-847
14Dedhar, S. (1994) Novel functions for calreticulin: interaction with integrins and modulation of gene expression? Trends Biochem Sci. 19, 269-271
15Raghavan, M., Wijeyesakere, S. J., Peters, L. R. and Del Cid, N. (2013) Calreticulin in the immune system: ins and outs. Trends Immunol. 34, 13-21
16Labriola, C., Cazzulo, J. J. and Parodi, A. J. (1999) Trypanosoma cruzi calreticulin is a lectin that binds monoglucosylated oligosaccharides but not protein moieties of glycoproteins. Mol Biol Cell. 10, 1381-1394
17Zapun, A., Darby, N. J., Tessier, D. C., Michalak, M., Bergeron, J. J. and Thomas, D. Y. (1998) Enhanced catalysis of ribonuclease B folding by the interaction of calnexin or calreticulin with ERp57. J Biol Chem. 273, 6009-6012
18Vassilakos, A., Michalak, M., Lehrman, M. A. and Williams, D. B. (1998) Oligosaccharide binding characteristics of the molecular chaperones calnexin and calreticulin. Biochemistry-Us. 37, 3480-3490
19Spiro, R. G., Zhu, Q., Bhoyroo, V. and Soling, H. D. (1996) Definition of the lectin-like properties of the molecular chaperone, calreticulin, and demonstration of its copurification with endomannosidase from rat liver Golgi. J Biol Chem. 271, 11588-11594
20Pozzan, T., Rizzuto, R., Volpe, P. and Meldolesi, J. (1994) Molecular and cellular physiology of intracellular calcium stores. Physiol Rev. 74, 595-636
21Meldolesi, J. and Pozzan, T. (1998) The endoplasmic reticulum Ca2+ store: a view from the lumen. Trends Biochem Sci. 23, 10-14
22Ostwald, T. J. and MacLennan, D. H. (1974) Isolation of a high affinity calcium-binding protein from sarcoplasmic reticulum. J Biol Chem. 249, 974-979
23Bastianutto, C., Clementi, E., Codazzi, F., Podini, P., De Giorgi, F., Rizzuto, R., Meldolesi, J. and Pozzan, T. (1995) Overexpression of calreticulin increases the Ca2+ capacity of rapidly exchanging Ca2+ stores and reveals aspects of their lumenal microenvironment and function. J Cell Biol. 130, 847-855
24Mery, L., Mesaeli, N., Michalak, M., Opas, M., Lew, D. P. and Krause, K. H. (1996) Overexpression of calreticulin increases intracellular Ca2+ storage and decreases store-operated Ca2+ influx. J Biol Chem. 271, 9332-9339
25Villagomez, M., Szabo, E., Podcheko, A., Feng, T., Papp, S. and Opas, M. (2009) Calreticulin and focal-contact-dependent adhesion. Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire. 87, 545-556
26Fadel, M. P., Dziak, E., Lo, C. M., Ferrier, J., Mesaeli, N., Michalak, M. and Opas, M. (1999) Calreticulin affects focal contact-dependent but not close contact-dependent cell-substratum adhesion. Journal of Biological Chemistry. 274, 15085-15094
27Lu, Y. C., Chen, C. N., Wang, B., Hsu, W. M., Chen, S. T., Chang, K. J., Chang, C. C. and Lee, H. (2011) Changes in tumor growth and metastatic capacities of J82 human bladder cancer cells suppressed by down-regulation of calreticulin expression. Am J Pathol. 179, 1425-1433
28Papp, S., Szabo, E., Kim, H., McCulloch, C. A. and Opas, M. (2008) Kinase-dependent adhesion to fibronectin: regulation by calreticulin. Exp Cell Res. 314, 1313-1326
29Opas, M., SzewczenkoPawlikowski, M., Jass, G. K., Mesaeli, N. and Michalak, M. (1996) Calreticulin modulates cell adhesiveness via regulation of vinculin expression. Journal of Cell Biology. 135, 1913-1923
30Papp, S., Fadel, M. P., Kim, H., McCulloch, C. A. and Opas, M. (2007) Calreticulin affects fibronectin-based cell-substratum adhesion via the regulation of c-Src activity. J Biol Chem. 282, 16585-16598
31Dedhar, S., Rennie, P. S., Shago, M., Hagesteijn, C. Y., Yang, H., Filmus, J., Hawley, R. G., Bruchovsky, N., Cheng, H., Matusik, R. J. and et al. (1994) Inhibition of nuclear hormone receptor activity by calreticulin. Nature. 367, 480-483
32Coppolino, M. G. and Dedhar, S. (1999) Ligand-specific, transient interaction between integrins and calreticulin during cell adhesion to extracellular matrix proteins is dependent upon phosphorylation dephosphorylation events. Biochem J. 340, 41-50
33Nickenig, G., Michaelsen, F., Muller, C., Berger, A., Vogel, T., Sachinidis, A., Vetter, H. and Bohm, M. (2002) Destabilization of AT(1) receptor mRNA by calreticulin. Circ Res. 90, 53-58
34Totary-Jain, H., Naveh-Many, T., Riahi, Y., Kaiser, N., Eckel, J. and Sasson, S. (2005) Calreticulin destabilizes glucose transporter-1 mRNA in vascular endothelial and smooth muscle cells under high-glucose conditions. Circ Res. 97, 1001-1008
35Zamanian, M., Veerakumarasivam, A., Abdullah, S. and Rosli, R. (2013) Calreticulin and cancer. Pathol Oncol Res. 19, 149-154
36Hsu, W. M., Hsieh, F. J., Jeng, Y. M., Kuo, M. L., Chen, C. N., Lai, D. M., Hsieh, L. J., Wang, B. T., Tsao, P. N., Lee, H., Lin, M. T., Lai, H. S. and Chen, W. J. (2005) Calreticulin expression in neuroblastoma--a novel independent prognostic factor. Ann Oncol. 16, 314-321
37Chen, C. N., Chang, C. C., Su, T. E., Hsu, W. M., Jeng, Y. M., Ho, M. C., Hsieh, F. J., Lee, P. H., Kuo, M. L., Lee, H. and Chang, K. J. (2009) Identification of calreticulin as a prognosis marker and angiogenic regulator in human gastric cancer. Ann Surg Oncol. 16, 524-533
38Lwin, Z. M., Guo, C., Salim, A., Yip, G. W., Chew, F. T., Nan, J., Thike, A. A., Tan, P. H. and Bay, B. H. (2010) Clinicopathological significance of calreticulin in breast invasive ductal carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 23, 1559-1566
39Vaksman, O., Davidson, B., Trope, C. and Reich, R. (2013) Calreticulin expression is reduced in high-grade ovarian serous carcinoma effusions compared with primary tumors and solid metastases. Human pathology. 44, 2677-2683
40Sheng, W., Chen, C., Dong, M., Zhou, J., Liu, Q., Dong, Q. and Li, F. (2014) Overexpression of calreticulin contributes to the development and progression of pancreatic cancer. J Cell Physiol. 229, 887-897
41Du, X. L., Hu, H., Lin, D. C., Xia, S. H., Shen, X. M., Zhang, Y., Luo, M. L., Feng, Y. B., Cai, Y., Xu, X., Han, Y. L., Zhan, Q. M. and Wang, M. R. (2007) Proteomic profiling of proteins dysregulted in Chinese esophageal squamous cell carcinoma. J Mol Med (Berl). 85, 863-875
42Chiang, W. F., Hwang, T. Z., Hour, T. C., Wang, L. H., Chiu, C. C., Chen, H. R., Wu, Y. J., Wang, C. C., Wang, L. F., Chien, C. Y., Chen, J. H., Hsu, C. T. and Chen, J. Y. (2013) Calreticulin, an endoplasmic reticulum-resident protein, is highly expressed and essential for cell proliferation and migration in oral squamous cell carcinoma. Oral oncology. 49, 534-541
43Chahed, K., Kabbage, M., Ehret-Sabatier, L., Lemaitre-Guillier, C., Remadi, S., Hoebeke, J. and Chouchane, L. (2005) Expression of fibrinogen E-fragment and fibrin E-fragment is inhibited in the human infiltrating ductal carcinoma of the breast: the two-dimensional electrophoresis and MALDI-TOF-mass spectrometry analyses. Int J Oncol. 27, 1425-1431
44Bini, L., Magi, B., Marzocchi, B., Arcuri, F., Tripodi, S., Cintorino, M., Sanchez, J. C., Frutiger, S., Hughes, G., Pallini, V., Hochstrasser, D. F. and Tosi, P. (1997) Protein expression profiles in human breast ductal carcinoma and histologically normal tissue. Electrophoresis. 18, 2832-2841
45Alfonso, P., Nunez, A., Madoz-Gurpide, J., Lombardia, L., Sanchez, L. and Casal, J. I. (2005) Proteomic expression analysis of colorectal cancer by two-dimensional differential gel electrophoresis. Proteomics. 5, 2602-2611
46Alaiya, A., Roblick, U., Egevad, L., Carlsson, A., Franzen, B., Volz, D., Huwendiek, S., Linder, S. and Auer, G. (2000) Polypeptide expression in prostate hyperplasia and prostate adenocarcinoma. Anal Cell Pathol. 21, 1-9
47Hellman, K., Alaiya, A. A., Schedvins, K., Steinberg, W., Hellstrom, A. C. and Auer, G. (2004) Protein expression patterns in primary carcinoma of the vagina. Brit J Cancer. 91, 319-326
48Minami, S., Nagashio, R., Ueda, J., Matsumoto, K., Goshima, N., Hattori, M., Hachimura, K., Iwamura, M. and Sato, Y. (2014) Detection of tumor-associated antigens in culture supernatants using autoantibodies in sera from patients with bladder cancer. Biomedical research (Tokyo, Japan). 35, 25-35
49Kageyama, S., Isono, T., Iwaki, H., Wakabayashi, Y., Okada, Y., Kotani, K., Yoshimura, K., Terai, A., Arai, Y. and Yoshiki, T. (2004) Identification by proteomic analysis of calreticulin as a marker for bladder cancer and evaluation of the diagnostic accuracy of its detection in urine. Clinical Chemistry. 50, 857-866
50Kageyama, S., Isono, T., Matsuda, S., Ushio, Y., Satomura, S., Terai, A., Arai, Y., Kawakita, M., Okada, Y. and Yoshiki, T. (2009) Urinary calreticulin in the diagnosis of bladder urothelial carcinoma. International Journal of Urology. 16, 481-486
51Gardai, S. J., McPhillips, K. A., Frasch, S. C., Janssen, W. J., Starefeldt, A., Murphy-Ullrich, J. E., Bratton, D. L., Oldenborg, P. A., Michalak, M. and Henson, P. M. (2005) Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell. 123, 321-334
52Obeid, M., Tesniere, A., Ghiringhelli, F., Fimia, G. M., Apetoh, L., Perfettini, J. L., Castedo, M., Mignot, G., Panaretakis, T., Casares, N., Metivier, D., Larochette, N., van Endert, P., Ciccosanti, F., Piacentini, M., Zitvogel, L. and Kroemer, G. (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 13, 54-61
53Chao, M. P., Jaiswal, S., Weissman-Tsukamoto, R., Alizadeh, A. A., Gentles, A. J., Volkmer, J., Weiskopf, K., Willingham, S. B., Raveh, T., Park, C. Y., Majeti, R. and Weissman, I. L. (2010) Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47. Science translational medicine. 2, 63ra94
54Clarke, C. and Smyth, M. J. (2007) Calreticulin exposure increases cancer immunogenicity. Nat Biotechnol. 25, 192-193
55Alur, M., Nguyen, M. M., Eggener, S. E., Jiang, F., Dadras, S. S., Stern, J., Kimm, S., Roehl, K., Kozlowski, J., Pins, M., Michalak, M., Dhir, R. and Wang, Z. (2009) Suppressive roles of calreticulin in prostate cancer growth and metastasis. Am J Pathol. 175, 882-890
56Shu, Q., Li, W., Li, H. and Sun, G. (2014) Vasostatin Inhibits VEGF-Induced Endothelial Cell Proliferation, Tube Formation and Induces Cell Apoptosis under Oxygen Deprivation. Int J Mol Sci. 15, 6019-6030
57Wu, M. F. F., Bai, X. Y. Y., Xu, G., Wei, J. C. C., Zhu, T., Zhang, Y. T., Li, Q., Liu, P., Song, A. P., Zhao, L. P., Gang, C., Han, Z. Q., Wang, S. X., Zhou, J. F., Lu, Y. P. and Ma, D. (2007) Proteome analysis of human androgen-independent prostate cancer cell lines: Variable metastatic potentials correlated with vimentin expression. Proteomics. 7, 1973-1983
58Leung-Hagesteijn, C. Y., Milankov, K., Michalak, M., Wilkins, J. and Dedhar, S. (1994) Cell attachment to extracellular matrix substrates is inhibited upon downregulation of expression of calreticulin, an intracellular integrin alpha-subunit-binding protein. J Cell Sci. 107 ( Pt 3), 589-600
59Coppolino, M. G., Woodside, M. J., Demaurex, N., Grinstein, S., St-Arnaud, R. and Dedhar, S. (1997) Calreticulin is essential for integrin-mediated calcium signalling and cell adhesion. Nature. 386, 843-847
60Coppolino, M., Leunghagesteijn, C., Dedhar, S. and Wilkins, J. (1995) Inducible Interaction of Integrin Alpha(2)Beta(1) with Calreticulin - Dependence on the Activation State of the Integrin. Journal of Biological Chemistry. 270, 23132-23138
61Coppolino, M. G. and Dedhar, S. (1999) Ligand-specific, transient interaction between integrins and calreticulin during cell adhesion to extracellular matrix proteins is dependent upon phosphorylation/dephosphorylation events. Biochem J. 340 ( Pt 1), 41-50
62Ihara, Y., Inai, Y. and Ikezaki, M. (2011) Alteration of integrin-dependent adhesion and signaling in EMT-like MDCK cells established through overexpression of calreticulin. J Cell Biochem. 112, 2518-2528
63Szabo, E., Papp, S. and Opas, M. (2007) Differential calreticulin affects focal contacts via the Calmodulin/CaMK II pathway. Journal of Cellular Physiology. 213, 269-277
64Goicoechea, S., Orr, A. W., Pallero, M. A., Eggleton, P. and Murphy-Ullrich, J. E. (2000) Thrombospondin mediates focal adhesion disassembly through interactions with cell surface calreticulin. J Biol Chem. 275, 36358-36368
65Miyoshi, E., Moriwaki, K. and Nakagawa, T. (2008) Biological function of fucosylation in cancer biology. J Biochem. 143, 725-729
66Turner, G. A. (1995) Haptoglobin. A potential reporter molecule for glycosylation changes in disease. Adv Exp Med Biol. 376, 231-238
67Mas, E., Pasqualini, E., Caillol, N., El Battari, A., Crotte, C., Lombardo, D. and Sadoulet, M. O. (1998) Fucosyltransferase activities in human pancreatic tissue: comparative study between cancer tissues and established tumoral cell lines. Glycobiology. 8, 605-613
68Baumann, H., Nudelman, E., Watanabe, K. and Hakomori, S. (1979) Neutral fucolipids and fucogangliosides of rat hepatoma HTC and H35 cells, rat liver, and hepatocytes. Cancer Res. 39, 2637-2643
69Ito, Y., Miyauchi, A., Yoshida, H., Uruno, T., Nakano, K., Takamura, Y., Miya, A., Kobayashi, K., Yokozawa, T., Matsuzuka, F., Taniguchi, N., Matsuura, N., Kuma, K. and Miyoshi, E. (2003) Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation. Cancer Lett. 200, 167-172
70Okuyama, N., Ide, Y., Nakano, M., Nakagawa, T., Yamanaka, K., Moriwaki, K., Murata, K., Ohigashi, H., Yokoyama, S., Eguchi, H., Ishikawa, O., Ito, T., Kato, M., Kasahara, A., Kawano, S., Gu, J., Taniguchi, N. and Miyoshi, E. (2006) Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation. Int J Cancer. 118, 2803-2808
71Madjd, Z., Parsons, T., Watson, N. F., Spendlove, I., Ellis, I. and Durrant, L. G. (2005) High expression of Lewis y/b antigens is associated with decreased survival in lymph node negative breast carcinomas. Breast Cancer Res. 7, R780-787
72Kim, Y. S., Itzkowitz, S. H., Yuan, M., Chung, Y., Satake, K., Umeyama, K. and Hakomori, S. (1988) Lex and Ley antigen expression in human pancreatic cancer. Cancer Res. 48, 475-482
73Cordon-Cardo, C., Reuter, V. E., Lloyd, K. O., Sheinfeld, J., Fair, W. R., Old, L. J. and Melamed, M. R. (1988) Blood group-related antigens in human urothelium: enhanced expression of precursor, LeX, and LeY determinants in urothelial carcinoma. Cancer Res. 48, 4113-4120
74Zhang, Z., Sun, P., Liu, J., Fu, L., Yan, J., Liu, Y., Yu, L., Wang, X. and Yan, Q. (2008) Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth. Biochim Biophys Acta. 1783, 287-296
75Mejias-Luque, R., Lopez-Ferrer, A., Garrido, M., Fabra, A. and de Bolos, C. (2007) Changes in the invasive and metastatic capacities of HT-29/M3 cells induced by the expression of fucosyltransferase 1. Cancer Science. 98, 1000-1005
76Janik, M. E., Litynska, A. and Vereecken, P. (2010) Cell migration-the role of integrin glycosylation. Biochim Biophys Acta. 1800, 545-555
77Zhao, Y., Sato, Y., Isaji, T., Fukuda, T., Matsumoto, A., Miyoshi, E., Gu, J. and Taniguchi, N. (2008) Branched N-glycans regulate the biological functions of integrins and cadherins. Febs J. 275, 1939-1948
78Guo, H. B., Lee, I., Kamar, M., Akiyama, S. K. and Pierce, M. (2002) Aberrant N-glycosylation of beta1 integrin causes reduced alpha5beta1 integrin clustering and stimulates cell migration. Cancer Res. 62, 6837-6845
79Gu, J., Zhao, Y., Isaji, T., Shibukawa, Y., Ihara, H., Takahashi, M., Ikeda, Y., Miyoshi, E., Honke, K. and Taniguchi, N. (2004) Beta1,4-N-Acetylglucosaminyltransferase III down-regulates neurite outgrowth induced by costimulation of epidermal growth factor and integrins through the Ras/ERK signaling pathway in PC12 cells. Glycobiology. 14, 177-186
80Zhao, Y., Itoh, S., Wang, X., Isaji, T., Miyoshi, E., Kariya, Y., Miyazaki, K., Kawasaki, N., Taniguchi, N. and Gu, J. (2006) Deletion of core fucosylation on alpha3beta1 integrin down-regulates its functions. J Biol Chem. 281, 38343-38350
81Jemal, A., Siegel, R., Ward, E., Hao, Y. P., Xu, J. Q. and Thun, M. J. (2009) Cancer Statistics, 2009. Ca-Cancer J Clin. 59, 225-249
82Prout, G. R. and Marshall, V. F. (1956) The Prognosis with Untreated Bladder Tumors. Cancer. 9, 551-558
83Yasui, W., Oue, N., Aung, P. P., Matsumura, S., Shutoh, M. and Nakayama, H. (2005) Molecular-pathological prognostic factors of gastric cancer: a review. Gastric Cancer. 8, 86-94
84Wang, Y., Liu, J., Smith, E., Zhou, K., Liao, J., Yang, G. Y., Tan, M. and Zhan, X. (2007) Downregulation of missing in metastasis gene (MIM) is associated with the progression of bladder transitional carcinomas. Cancer Invest. 25, 79-86
85Kleeff, J., Kornmann, M., Sawhney, H. and Korc, M. (2000) Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells. Int J Cancer. 86, 399-407
86Papp, S., Fadel, M. P., Kim, H., McCulloch, C. A. and Opas, M. (2007) Calreticulin affects fibronectin-based cell-substratum adhesion via the regulation of c-Src activity. Journal of Biological Chemistry. 282, 16585-16598
87Gu, J. and Taniguchi, N. (2004) Regulation of integrin functions by N-glycans. Glycoconj J. 21, 9-15
88Yan, L. M., Lin, B., Zhu, L. C., Hao, Y. Y., Qi, Y., Wang, C. Z., Gao, S., Liu, S. C., Zhang, S. L. and Iwamori, M. (2010) Enhancement of the adhesive and spreading potentials of ovarian carcinoma RMG-1 cells due to increased expression of integrin alpha5beta1 with the Lewis Y-structure on transfection of the alpha1,2-fucosyltransferase gene. Biochimie. 92, 852-857
89Chang, H. H., Chen, C. H., Chou, C. H., Liao, Y. F., Huang, M. J., Chen, Y. H., Wang, W. J., Huang, J., Hung, J. S., Ho, W. L., Jeng, Y. M., Che, M. I., Lee, H., Lu, M. Y., Yang, Y. L., Jou, S. T., Lin, D. T., Lin, K. H., Hsu, W. M. and Huang, M. C. (2013) beta-1,4-galactosyltransferase III enhances invasive phenotypes via beta1 integrin and predicts poor prognosis in neuroblastoma. Clin Cancer Res
90Lee, S. H., Hatakeyama, S., Yu, S. Y., Bao, X., Ohyama, C., Khoo, K. H., Fukuda, M. N. and Fukuda, M. (2009) Core3 O-glycan synthase suppresses tumor formation and metastasis of prostate carcinoma PC3 and LNCaP cells through down-regulation of alpha2beta1 integrin complex. J Biol Chem. 284, 17157-17169
91Misquitta, C. M., Chen, T. and Grover, A. K. (2006) Control of protein expression through mRNA stability in calcium signalling. Cell Calcium. 40, 329-346
92Barreau, C., Paillard, L. and Osborne, H. B. (2005) AU-rich elements and associated factors: are there unifying principles? Nucleic Acids Res. 33, 7138-7150
93Xu, N., Chen, C. Y. and Shyu, A. B. (1997) Modulation of the fate of cytoplasmic mRNA by AU-rich elements: key sequence features controlling mRNA deadenylation and decay. Mol Cell Biol. 17, 4611-4621
94Beelman, C. A. and Parker, R. (1995) Degradation of mRNA in eukaryotes. Cell. 81, 179-183
95Gold, L. I., Eggleton, P., Sweetwyne, M. T., Van Duyn, L. B., Greives, M. R., Naylor, S. M., Michalak, M. and Murphy-Ullrich, J. E. (2010) Calreticulin: non-endoplasmic reticulum functions in physiology and disease. Faseb Journal. 24, 665-683
96Schardt, J. A., Eyholzer, M., Timchenko, N. A., Mueller, B. U. and Pabst, T. (2010) Unfolded protein response suppresses CEBPA by induction of calreticulin in acute myeloid leukaemia. J Cell Mol Med. 14, 1509-1519
97Boden, G. and Merali, S. (2011) Measurement of the increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Methods Enzymol. 489, 67-82
98Lee, J. Y., Chang, J. W., Yang, W. S., Kim, S. B., Park, S. K., Park, J. S. and Lee, S. K. (2011) Albumin-induced epithelial-mesenchymal transition and ER stress are regulated through a common ROS-c-Src kinase-mTOR pathway: Effect of imatinib mesylate. Am J Physiol Renal Physiol
99Pike, S. E., Yao, L., Jones, K. D., Cherney, B., Appella, E., Sakaguchi, K., Nakhasi, H., Teruya-Feldstein, J., Wirth, P., Gupta, G. and Tosato, G. (1998) Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth. J Exp Med. 188, 2349-2356
100Pike, S. E., Yao, L., Setsuda, J., Jones, K. D., Cherney, B., Appella, E., Sakaguchi, K., Nakhasi, H., Atreya, C. D., Teruya-Feldstein, J., Wirth, P., Gupta, G. and Tosato, G. (1999) Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth. Blood. 94, 2461-2468
101Cai, K. X., Tse, L. Y., Leung, C., Tam, P. K. H., Xu, R. A. and Sham, M. H. (2008) Suppression of lung tumor growth and metastasis in mice by adeno-associated virus-mediated expression of vasostatin. Clinical Cancer Research. 14, 939-949
102Mesaeli, N. and Phillipson, C. (2004) Impaired p53 expression, function, and nuclear localization in calreticulin-deficient cells. Mol Biol Cell. 15, 1862-1870
103Lim, S., Chang, W., Lee, B. K., Song, H., Hong, J. H., Lee, S., Song, B. W., Kim, H. J., Cha, M. J., Jang, Y., Chung, N., Choi, S. Y. and Hwang, K. C. (2008) Enhanced calreticulin expression promotes calcium-dependent apoptosis in postnatal cardiomyocytes. Mol Cells. 25, 390-396
104Nanney, L. B., Woodrell, C. D., Greives, M. R., Cardwell, N. L., Pollins, A. C., Bancroft, T. A., Chesser, A., Michalak, M., Rahman, M., Siebert, J. W. and Gold, L. I. (2008) Calreticulin enhances porcine wound repair by diverse biological effects. American Journal of Pathology. 173, 610-630
105Liu, M. H., Imam, H., Oberg, K. and Zhou, Y. H. (2005) Gene transfer of vasostatin, a calreticulin fragment, into neuroendocrine tumor cells results in enhanced malignant behavior. Neuroendocrinology. 82, 1-10
106Papp, S., Fadel, M. P. and Opas, M. (2007) Dissecting focal adhesions in cells differentially expressing calreticulin: a microscopy study. Biology of the Cell. 99, 389-402
107Szabo, E., Feng, T. S., Dziak, E. and Opas, M. (2009) Cell Adhesion and Spreading Affect Adipogenesis from Embryonic Stem Cells: The Role of Calreticulin. Stem Cells. 27, 2092-2102
108Leunghagesteijn, C. Y., Milankov, K., Michalak, M., Wilkins, J. and Dedhar, S. (1994) Cell Attachment to Extracellular-Matrix Substrates Is Inhibited Upon down-Regulation of Expression of Calreticulin, an Intracellular Integrin Alpha-Subunit-Binding Protein. J Cell Sci. 107, 589-600
109Elton, C. M., Smethurst, P. A., Eggleton, P. and Farndale, R. W. (2002) Physical and functional interaction between cell-surface calreticulin and the collagen receptors integrin alpha 2 beta 1 and glycoprotein VI in human platelets. Thromb Haemostasis. 88, 648-654
110Rathinam, R. and Alahari, S. K. (2010) Important role of integrins in the cancer biology. Cancer Metast Rev. 29, 223-237
111Alur, M., Nguyen, M. M., Eggener, S. E., Jiang, F., Dadras, S. S., Stern, J., Kimm, S., Roehl, K., Kozlowski, J., Pins, M., Michalak, M., Dhir, R. and Wang, Z. (2009) Suppressive Roles of Calreticulin in Prostate Cancer Growth and Metastasis. American Journal of Pathology. 175, 882-890
112Hanks, S. K., Ryzhova, L., Shin, N. Y. and Brabek, J. (2003) Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility. Front Biosci. 8, D982-D996
113Daniel, J. M. and Reynolds, A. B. (1997) Tyrosine phosphorylation and cadherin/catenin function. Bioessays. 19, 883-891
114Schaller, M. D. (2001) Paxillin: a focal adhesion-associated adaptor protein. Oncogene. 20, 6459-6472
115Cai, H., Zhang, T., Tang, W. X. and Li, S. L. (2010) [Expression of paxillin in breast cancer cell with high and low metastatic potentiality]. Sichuan Da Xue Xue Bao Yi Xue Ban. 41, 91-94
116Hanks, S. K. and Polte, T. R. (1997) Signaling through focal adhesion kinase. Bioessays. 19, 137-145
117Guhaniyogi, J. and Brewer, G. (2001) Regulation of mRNA stability in mammalian cells. Gene. 265, 11-23
118Gray, L. C., Hughes, T. R. and van den Berg, C. W. (2010) Binding of human antigen R (HuR) to an AU-rich element (ARE) in the 3''untranslated region (3''UTR) reduces the expression of decay accelerating factor (DAF). Mol Immunol. 47, 2545-2551
119Peng, S. S., Chen, C. Y. and Shyu, A. B. (1996) Functional characterization of a non-AUUUA AU-rich element from the c-jun proto-oncogene mRNA: evidence for a novel class of AU-rich elements. Mol Cell Biol. 16, 1490-1499
120Nanbu, R., Montero, L., D''Orazio, D. and Nagamine, Y. (1997) Enhanced stability of urokinase-type plasminogen activator mRNA in metastatic breast cancer MDA-MB-231 cells and LLC-PK1 cells down-regulated for protein kinase C--correlation with cytoplasmic heterogeneous nuclear ribonucleoprotein C. Eur J Biochem. 247, 169-174
121Fini, M. E., Plucinska, I. M., Mayer, A. S., Gross, R. H. and Brinckerhoff, C. E. (1987) A gene for rabbit synovial cell collagenase: member of a family of metalloproteinases that degrade the connective tissue matrix. Biochemistry-Us. 26, 6156-6165
122Nanbu, R., Menoud, P. A. and Nagamine, Y. (1994) Multiple instability-regulating sites in the 3'' untranslated region of the urokinase-type plasminogen activator mRNA. Mol Cell Biol. 14, 4920-4928
123Lee, H. H., Kim, W. T., Kim, D. H., Park, J. W., Kang, T. H., Chung, J. W. and Leem, S. H. (2013) Tristetraprolin suppresses AHRR expression through mRNA destabilization. Febs Lett. 587, 1518-1523
124Xu, N., Chen, C. Y. and Shyu, A. B. (2001) Versatile role for hnRNP D isoforms in the differential regulation of cytoplasmic mRNA turnover. Mol Cell Biol. 21, 6960-6971
125Sarkar, B., Xi, Q., He, C. and Schneider, R. J. (2003) Selective degradation of AU-rich mRNAs promoted by the p37 AUF1 protein isoform. Mol Cell Biol. 23, 6685-6693
126Levy, N. S., Chung, S., Furneaux, H. and Levy, A. P. (1998) Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR. J Biol Chem. 273, 6417-6423
127Zhang, J. and Chen, Q. M. (2013) Far upstream element binding protein 1: a commander of transcription, translation and beyond. Oncogene. 32, 2907-2916
128Irwin, N., Baekelandt, V., Goritchenko, L. and Benowitz, L. I. (1997) Identification of two proteins that bind to a pyrimidine-rich sequence in the 3''-untranslated region of GAP-43 mRNA. Nucleic Acids Res. 25, 1281-1288
129Chien, H. L., Liao, C. L. and Lin, Y. L. (2011) FUSE binding protein 1 interacts with untranslated regions of Japanese encephalitis virus RNA and negatively regulates viral replication. J Virol. 85, 4698-4706
130Moriwaki, K., Noda, K., Furukawa, Y., Ohshima, K., Uchiyama, A., Nakagawa, T., Taniguchi, N., Daigo, Y., Nakamura, Y., Hayashi, N. and Miyoshi, E. (2009) Deficiency of GMDS leads to escape from NK cell-mediated tumor surveillance through modulation of TRAIL signaling. Gastroenterology. 137, 188-198
131Moriwaki, K., Shinzaki, S. and Miyoshi, E. (2011) GDP-mannose-4,6-dehydratase (GMDS) deficiency renders colon cancer cells resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor- and CD95-mediated apoptosis by inhibiting complex II formation. J Biol Chem. 286, 43123-43133
132Zhu, J., Wang, Y., Yu, Y., Wang, Z., Zhu, T., Xu, X., Liu, H., Hawke, D., Zhou, D. and Li, Y. (2013) Aberrant fucosylation of glycosphingolipids in human hepatocellular carcinoma tissues. Liver Int
133Mehta, A. and Block, T. M. (2008) Fucosylated glycoproteins as markers of liver disease. Dis Markers. 25, 259-265
134Kaczmarek, R. (2010) [Alterations of Lewis histo-blood group antigen expression in cancer cells]. Postepy Hig Med Dosw (Online). 64, 87-99
135Numahata, K., Satoh, M., Handa, K., Saito, S., Ohyama, C., Ito, A., Takahashi, T., Hoshi, S., Orikasa, S. and Hakomori, S. I. (2002) Sialosyl-Le(x) expression defines invasive and metastatic properties of bladder carcinoma. Cancer. 94, 673-685
136Gu, J., Isaji, T., Xu, Q., Kariya, Y., Gu, W., Fukuda, T. and Du, Y. (2012) Potential roles of N-glycosylation in cell adhesion. Glycoconj J. 29, 599-607
137Rambaruth, N. D. and Dwek, M. V. (2011) Cell surface glycan-lectin interactions in tumor metastasis. Acta Histochem. 113, 591-600


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