Sweet and sour: The impact of differential glycosylation in cancer cells undergoing epithelial-mesenchymal transition

Frontiers in Oncology

Volumn 4 MAR, Issue , 2014, Pages

  Freire de Lima, Leonardo ^a  

^a FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

Cancer; Epithelial mesenchymal transition; Extracellular matrix; Glycosylation; Glycosyltransferases; Metastasis; Oncofetal fibronectin

Indexed keywords

FIBRONECTIN; GLYCAN; MUCIN 1; SIALOMUCIN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA; CA 125 ANTIGEN; CARCINOEMBRYONIC ANTIGEN; GLYCOSYLTRANSFERASE; LEUKOSIALIN; MATRIX METALLOPROTEINASE; N ACETYLGLUCOSAMINE; ONCOFETAL ANTIGEN; PROSTATE SPECIFIC ANTIGEN; SERINE; THREONINE;

BIOLOGICAL ACTIVITY; CANCER CELL; CELL INVASION; CELL MIGRATION; CELL PROLIFERATION; ENZYME SYNTHESIS; EPITHELIAL MESENCHYMAL TRANSITION; EXTRACELLULAR MATRIX; GENE EXPRESSION; GENOTYPE; GLYCOSYLATION; HOMEOSTASIS; HOST PATHOGEN INTERACTION; HUMAN; HYPERGLYCEMIA; METASTASIS; RECOGNITION; REVIEW; TUMOR GROWTH; UPREGULATION; CANCER GROWTH; CANCER RESEARCH; CARCINOGENESIS; CELL FUNCTION; DNA REPAIR; GENE SILENCING; GLYCOBIOLOGY; HEMOSTASIS; MORPHOGENESIS; PROTEIN EXPRESSION; PROTEIN GLYCOSYLATION; PROTEIN PROCESSING; SOMATIC MUTATION;

EID: 84901004695     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2014.00059     Document Type: Review

References (130)

1. Birchmeier W, Behrens J, Weidner KM, Hulsken J, Birchmeier C. Epithelial differentiation and the control of metastasis in carcinomas. Curr Top Microbiol Immunol (1996) 213(Pt 2):117-35.
2. Alfoldi J, Lindblad-Toh K. Comparative genomics as a tool to understand evolution and disease. Genome Res (2013) 23(7):1063-8. doi: 10.1101/gr.157503.113.
3. Karve TM, Cheema AK. Small changes huge impact: the role of protein posttranslational modifications in cellular homeostasis and disease. J Amino Acids (2011) 2011:207691. doi:10.4061/2011/207691.
4. Seo J, Lee KJ. Post-translational modifications and their biological functions: proteomic analysis and systematic approaches. J Biochem Mol Biol (2004) 37(1):35-44. doi:10.5483/BMBRep.2004.37.1.035.
5. Woodsmith J, Kamburov A, Stelzl U. Dual coordination of post translational modifications in human protein networks. PLoS Comput Biol (2013) 9(3):e1002933. doi:10.1371/journal.pcbi.1002933.
6. Schuldt A. Post-translational modification: a SUMO protease for stress protection. Nat Rev Mol Cell Biol (2013) 14(5):263. doi:10.1038/nrm3569.
7. Spiro RG. Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds. Glycobiology (2002) 12(4):43R-56R. doi:10.1093/glycob/12.4.43R.
8. Hakomori S. Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives. Cancer Res (1985) 45:2405-14.
9. Hakomori S. Glycosylation defining cancer malignancy: new wine in an old bottle. Proc Natl Acad Sci U S A (2002) 99(16):10231-3. doi:10.1073/pnas.172380699.
10. Kim YJ, Varki A. Perspectives on the significance of altered glycosylation of glycoproteins in cancer. Glycoconj J (1997) 14(5):569-76. doi:10.1023/A:1018580324971.
11. Ono M, Hakomori S. Glycosylation defining cancer cell motility and invasiveness. Glycoconj J (2004) 20(1):71-8. doi:10.1023/B:GLYC.0000018019.22070.7d.
12. Park S-Y, Yoon S-J, Freire-de-Lima L, Kim J-H, Hakomori S. Control of cell motility by interaction of gangliosides, tetraspanins, and epidermal growth factor receptor in A431 vs. KB epidermoid tumor cells. Carbohydr Res (2009) 344(12):1479-86. doi:10.1016/j.carres.2009.04.032.
13. Peracaula R, Barrabes S, Sarrats A, Rudd PM, de Llorens R. Altered glycosylation in tumours focused to cancer diagnosis. Dis Markers (2008) 25(4-5):207-18. doi:10.1155/2008/797629.
14. Meany DL, Chan DW. Aberrant glycosylation associated with enzymes as cancer biomarkers. Clin Proteomics (2011) 8(1):7. doi:10.1186/1559-0275-8-7.
15. Drake PM, Cho W, Li B, Prakobphol A, Johansen E, Anderson NL, et al. Sweetening the pot: adding glycosylation to the biomarker discovery equation. Clin Chem (2010) 56(2):223-36. doi:10.1373/clinchem.2009.136333.
16. Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem (2001) 47(4):624-30.
17. Peracaula R, Tabares G, Royle L, Harvey DJ, Dwek RA, Rudd PM, et al. Altered glycosylation pattern allows the distinction between prostate-specific antigen (PSA) from normal and tumor origins. Glycobiology (2003) 13(6):457-70. doi:10.1093/glycob/cwg041.
18. Saldova R, Struwe WB, Wynne K, Elia G, Duffy MJ, Rudd PM. Exploring the glycosylation of serum CA125. Int J Mol Sci (2013) 14(8):15636-54. doi:10.3390/ijms140815636.
19. Weerapana E, Imperiali B. Asparagine-linked protein glycosylation: from eukaryotic to prokaryotic systems. Glycobiology (2006) 16(6):91R-101R. doi:10.1093/glycob/cwj099.
20. Kleene R, Schachner M. Glycans and neural cell interactions. Nat Rev Neurosci (2004) 5(3):195-208. doi:10.1038/nrn1349.
21. Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell (2006) 126(5):855-67.
22. Freire-de-Lima L, Oliveira IA, Neves JL, Penha LL, Alisson-Silva F, Dias WB, et al. Sialic acid: a sweet swing between mammalian host and Trypanosoma cruzi. Front Immunol (2012) 3:356. doi:10.3389/fimmu.2012.00356.
23. Szymanski CM, Wren BW. Protein glycosylation in bacterial mucosal pathogens. Nat Rev Microbiol (2005) 3(3):225-37. doi:10.1038/nrmicro1100.
24. Freire-de-Lima L, Alisson-Silva F, Carvalho ST, Takiya CM, Rodrigues MM, DosReis GA, et al. Trypanosoma cruzi subverts host cell sialylation and may compromise antigen-specific CD8+ T cell responses. J Biol Chem (2010) 285(18):13388-96. doi:10.1074/jbc.M109.096305.
25. Marth JD, Grewal PK. Mammalian glycosylation in immunity. Nat Rev Immunol (2008) 8(11):874-87. doi:10.1038/nri2417.
26. Dube DH, Bertozzi CR. Glycans in cancer and inflammation-potential for therapeutics and diagnostics. Nat Rev Drug Discov (2005) 4(6):477-88. doi:10.1038/nrd1751.
27. Mueller MM, Fusenig NE. Friends or foes-bipolar effects of the tumour stroma in cancer. Nat Rev Cancer (2004) 4(11):839-49. doi:10.1038/nrc1477.
28. Lau KS, Dennis JW. N-glycans in cancer progression. Glycobiology (2008) 18(10):750-60. doi:10.1093/glycob/cwn071.
29. Taniguchi N, Korekane H. Branched N-glycans and their implications for cell adhesion, signaling and clinical applications for cancer biomarkers and in therapeutics. BMB Rep (2011) 44(12):772-81. doi:10.5483/BMBRep.2011.44.12.772.
30. Tian E, Ten Hagen KG. Recent insights into the biological roles of mucin-type O-glycosylation. Glycoconj J (2009) 26(3):325-34. doi:10.1007/s10719-008-9162-4.
31. Tsuboi S, Hatakeyama S, Ohyama C, Fukuda M. Two opposing roles of O-glycans in tumor metastasis. Trends Mol Med (2012) 18(4):224-32. doi:10.1016/j.molmed.2012.02.001.
32. Patsos G, Andre S, Roeckel N, Gromes R, Gebert J, Kopitz J, et al. Compensation of loss of protein function in microsatellite-unstable colon cancer cells (HCT116): a gene-dependent effect on the cell surface glycan profile. Glycobiology (2009) 19(7):726-34. doi:10.1093/glycob/cwp040.
33. Gill DJ, Clausen H, Bard F. Location, location, location: new insights into O-GalNAc protein glycosylation. Trends Cell Biol (2011) 21(3):149-58. doi:10.1016/j.tcb.2010.11.004.
34. Ju T, Wang Y, Aryal RP, Lehoux SD, Ding X, Kudelka MR, et al. Tn and sialyl-Tn antigens, aberrant O-glycomics as human disease markers. Proteomics Clin Appl (2013) 7(9-10):618-31. doi:10.1002/prca.201300024.
35. Fernandez-Rodriguez J, Feijoo-Carnero C, Merino-Trigo A, Paez de la Cadena M, Rodriguez-Berrocal FJ, de Carlos A, et al. Immunohistochemical analysis of sialic acid and fucose composition in human colorectal adenocarcinoma. Tumour Biol (2000) 21(3):153-64. doi:10.1159/000030122.
36. Bathi RJ, Nandimath K, Kannan N, Shetty P. Evaluation of glycoproteins as prognosticators in head and neck malignancy. Indian J Dent Res (2001) 12(2):93-9.
37. Dennis JW, Laferte S. Tumor cell surface carbohydrate and the metastatic phenotype. Cancer Metastasis Rev (1987) 5(3):185-204. doi:10.1007/BF00046998.
38. Handa K, Hakomori SI. Carbohydrate to carbohydrate interaction in development process and cancer progression. Glycoconj J (2012) 29(8-9):627-37. doi:10.1007/s10719-012-9380-7.
39. Baldus SE, Engelmann K, Hanisch FG. MUC1 and the MUCs: a family of human mucins with impact in cancer biology. Crit Rev Clin Lab Sci (2004) 41(2):189-231. doi:10.1080/10408360490452040.
40. Pinho S, Marcos NT, Ferreira B, Carvalho AS, Oliveira MJ, Santos-Silva F, et al. Biological significance of cancer-associated sialyl-Tn antigen: modulation of malignant phenotype in gastric carcinoma cells. Cancer Lett (2007) 249(2):157-70. doi:10.1016/j.canlet.2006.08.010.
41. Pinto R, Carvalho AS, Conze T, Magalhaes A, Picco G, Burchell JM, et al. Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation. J Cell Mol Med (2012) 16(7):1474-84. doi:10.1111/j.1582-4934.2011.01436.x.
42. Mazal D, Lo-Man R, Bay S, Pritsch O, Deriaud E, Ganneau C, et al. Monoclonal antibodies toward different Tn-amino acid backbones display distinct recognition patterns on human cancer cells. Implications for effective immuno-targeting of cancer. Cancer Immunol Immunother (2013) 62(6):1107-22. doi:10.1007/s00262-013-1425-7.
43. Kudo T, Ikehara Y, Togayachi A, Morozumi K, Watanabe M, Nakamura M, et al. Up-regulation of a set of glycosyltransferase genes in human colorectal cancer. Lab Invest (1998) 78(7):797-811.
44. Tarp MA, Clausen H. Mucin-type O-glycosylation and its potential use in drug and vaccine development. Biochim Biophys Acta (2008) 1780(3):546-63. doi:10.1016/j.bbagen.2007.09.010.
45. Wu YM, Nowack DD, Omenn GS, Haab BB. Mucin glycosylation is altered by pro-inflammatory signaling in pancreatic-cancer cells. J Proteome Res (2009) 8(4):1876-86. doi:10.1021/pr8008379.
46. Deguchi T, Tanemura M, Miyoshi E, Nagano H, Machida T, Ohmura Y, et al. Increased immunogenicity of tumor-associated antigen, mucin 1, engineered to express alpha-gal epitopes: a novel approach to immunotherapy in pancreatic cancer. Cancer Res (2010) 70(13):5259-69. doi:10.1158/0008-5472.CAN-09-4313.
47. Yu LG, Andrews N, Zhao Q, McKean D, Williams JF, Connor LJ, et al. Galectin-3 interaction with Thomsen-Friedenreich disaccharide on cancer-associated MUC1 causes increased cancer cell endothelial adhesion. J Biol Chem (2007) 282(1):773-81. doi:10.1074/jbc.M606862200.
48. Cascio S, Farkas AM, Hughey RP, Finn OJ. Altered glycosylation of MUC1 influences its association with CIN85: the role of this novel complex in cancer cell invasion and migration. Oncotarget (2013) 4(10):1686-97.
49. Wang ZQ, Bachvarova M, Morin C, Plante M, Gregoire J, Renaud MC, et al. Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation. Oncotarget (2014) 5(2):544-60.
50. Bennett EP, Hassan H, Mandel U, Hollingsworth MA, Akisawa N, Ikematsu Y, et al. Cloning and characterization of a close homologue of human UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6. Evidence for genetic but not functional redundancy. J Biol Chem (1999) 274(36):25362-70. doi:10.1074/jbc.274.36.25362.
51. Gnemmi V, Bouillez A, Gaudelot K, Hemon B, Ringot B, Pottier N, et al. MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/beta-catenin pathway and interaction with SNAIL promoter. Cancer Lett (2013). doi:10.1016/j.canlet.2013.12.029.
52. Ponnusamy MP, Seshacharyulu P, Lakshmanan I, Vaz AP, Chugh S, Batra SK. Emerging role of mucins in epithelial to mesenchymal transition. Curr Cancer Drug Targets (2013) 13(9):945-56. doi:10.2174/15680096113136660100.
53. Rajabi H, Alam M, Takahashi H, Kharbanda A, Guha M, Ahmad R, et al. MUC1-C oncoprotein activates the ZEB1/miR-200c regulatory loop and epithelial-mesenchymal transition. Oncogene (2013). doi:10.1038/onc.2013.114.
54. Roy LD, Sahraei M, Subramani DB, Besmer D, Nath S, Tinder TL, et al. MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition. Oncogene (2011) 30(12):1449-59. doi:10.1038/onc.2010.526.
55. Sikut R, Nilsson O, Baeckstrom D, Hansson GC. Colon adenoma and cancer cells aberrantly express the leukocyte-associated sialoglycoprotein CD43. Biochem Biophys Res Commun (1997) 238(2):612-6. doi:10.1006/bbrc.1997.7334.
56. Fu Q, Cash SE, Andersen JJ, Kennedy CR, Oldenburg DG, Zander VB, et al. CD43 in the nucleus and cytoplasm of lung cancer is a potential therapeutic target. Int J Cancer (2013) 132(8):1761-70. doi:10.1002/ijc.27873.
57. Bendas G, Borsig L. Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins. Int J Cell Biol (2012) 2012:676731. doi:10.1155/2012/676731.
58. Gil-Bernabe AM, Lucotti S, Muschel RJ. Coagulation and metastasis: what does the experimental literature tell us? Br J Haematol (2013) 162(4):433-41. doi:10.1111/bjh.12381.
59. Wirtz D, Konstantopoulos K, Searson PC. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer (2011) 11(7):512-22. doi:10.1038/nrc3080.
60. Konstantopoulos K, Thomas SN. Cancer cells in transit: the vascular interactions of tumor cells. Annu Rev Biomed Eng (2009) 11:177-202. doi:10.1146/annurev-bioeng-061008-124949.
61. Ugorski M, Laskowska A. Sialyl Lewis(a): a tumor-associated carbohydrate antigen involved in adhesion and metastatic potential of cancer cells. Acta Biochim Pol (2002) 49(2):303-11.
62. Sozzani P, Arisio R, Porpiglia M, Benedetto C. Is Sialyl Lewis x antigen expression a prognostic factor in patients with breast cancer? Int J Surg Pathol (2008) 16(4):365-74. doi:10.1177/1066896908324668.
63. Sayat R, Leber B, Grubac V, Wiltshire L, Persad S. O-GlcNAc-glycosylation of beta-catenin regulates its nuclear localization and transcriptional activity. Exp Cell Res (2008) 314(15):2774-87. doi:10.1016/j.yexcr.2008.05.017.
64. Jin FZ, Yu C, Zhao DZ, Wu MJ, Yang Z. A correlation between altered O-GlcNAcylation, migration and with changes in E-cadherin levels in ovarian cancer cells. Exp Cell Res (2013) 319(10):1482-90. doi:10.1016/j.yexcr.2013.03.013.
65. Park SY, Kim HS, Kim NH, Ji S, Cha SY, Kang JG, et al. Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition. EMBO J (2010) 29(22):3787-96. doi:10.1038/emboj.2010.254.
66. Bei R, Mizejewski GJ. Alpha fetoprotein is more than a hepatocellular cancer biomarker: from spontaneous immune response in cancer patients to the development of an AFP-based cancer vaccine. Curr Mol Med (2011) 11(7):564-81. doi:10.2174/156652411800615162.
67. Amri R, Bordeianou LG, Sylla P, Berger DL. Preoperative carcinoembryonic antigen as an outcome predictor in colon cancer. J Surg Oncol (2013) 108(1):14-8. doi:10.1002/jso.23352.
68. Matsuura H, Hakomori S. The oncofetal domain of fibronectin defined by monoclonal antibody FDC-6: its presence in fibronectins from fetal and tumor tissues and its absence in those from normal adult tissues and plasma. Proc Natl Acad Sci U S A (1985) 82(19):6517-21. doi:10.1073/pnas.82.19.6517.
69. Egeblad M, Nakasone ES, Werb Z. Tumors as organs: complex tissues that interface with the entire organism. Dev Cell (2010) 18(6):884-901. doi:10.1016/j.devcel.2010.05.012.
70. Xie K, Abbruzzese JL. Developmental biology informs cancer: the emerging role of the hedgehog signaling pathway in upper gastrointestinal cancers. Cancer Cell (2003) 4(4):245-7. doi:10.1016/S1535-6108(03)00246-0.
71. Radtke F, Clevers H. Self-renewal and cancer of the gut: two sides of a coin. Science (2005) 307(5717):1904-9. doi:10.1126/science.1104815.
72. Bissell MJ, Radisky D. Putting tumours in context. Nat Rev Cancer (2001) 1(1):46-54. doi:10.1038/35094059.
73. Wiseman BS, Werb Z. Stromal effects on mammary gland development and breast cancer. Science (2002) 296(5570):1046-9. doi:10.1126/science.1067431.
74. Bissell MJ, Labarge MA. Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment? Cancer Cell (2005) 7(1):17-23. doi:10.1016/j.ccr.2004.12.013.
75. Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression. Nature (2004) 432(7015):332-7. doi:10.1038/nature03096.
76. Sternlicht MD, Lochter A, Sympson CJ, Huey B, Rougier JP, Gray JW, et al. The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell (1999) 98(2):137-46.
77. Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, et al. Tensional homeostasis and the malignant phenotype. Cancer Cell (2005) 8(3):241-54. doi:10.1016/j.ccr.2005.08.010.
78. Erler JT, Weaver VM. Three-dimensional context regulation of metastasis. Clin Exp Metastasis (2009) 26(1):35-49. doi:10.1007/s10585-008-9209-8.
79. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell (2009) 139(5):891-906. doi:10.1016/j.cell.2009.10.027.
80. Matsuura H, Takio K, Titani K, Greene T, Levery SB, Salyan MEK, et al. The oncofetal structure of human fibronectin defined by monoclonal antibody FDC-6: unique structural requirement for the antigenic specificity provided by a glycosylhexapeptide. J Biol Chem (1988) 263(7):3314-22.
81. Matsuura H, Greene T, Hakomori S. An alpha-N-acetylgalactosaminylation at the threonine residue of a defined peptide sequence creates the oncofetal peptide epitope in human fibronectin. J Biol Chem (1989) 264(18):10472-6.
82. White ES, Muro AF. Fibronectin splice variants: understanding their multiple roles in health and disease using engineered mouse models. IUBMB Life (2011) 63(7):538-46. doi:10.1002/iub.493.
83. Inufusa H, Nakamura M, Adachi T, Nakatani Y, Shindo K, Yasutomi M, et al. Localization of oncofetal and normal fibronectin in colorectal cancer. Correlation with histologic grade, liver metastasis, and prognosis. Cancer (1995) 75(12):2802-8. doi:10.1002/1097-0142(19950615)75:12<2802::AID-CNCR2820751204>3.0.CO;2-O.
84. Loridon-Rosa B, Vielh P, Matsuura H, Clausen H, Cuadrado C, Burtin P. Distribution of oncofetal fibronectin in human mammary tumors: immunofluorescence study on histological sections. Cancer Res (1990) 50:1608-12.
85. Mandel U, Gaggero B, Reibel J, Therkildsen MH, Dabelsteen E, Clausen H. Oncofetal fibronectins in oral carcinomas: correlation of two different types. APMIS (1994) 102(9):695-702. doi:10.1111/j.1699-0463.1994.tb05222.x.
86. Freire-de-Lima L, Gelfenbeyn K, Ding Y, Mandel U, Clausen H, Handa K, et al. Involvement of O-glycosylation defining oncofetal fibronectin in epithelial-mesenchymal transition process. Proc Natl Acad Sci U S A (2011) 108(43):17690-5. doi:10.1073/pnas.1115191108.
87. Ding Y, Gelfenbeyn K, Freire-de-Lima L, Handa K, Hakomori SI. Induction of epithelial-mesenchymal transition with O-glycosylated oncofetal fibronectin. FEBS Lett (2012) 586(13):1813-20. doi:10.1016/j.febslet.2012.05.020.
88. Alisson-Silva F, Freire-de-Lima L, Donadio JL, Lucena MC, Penha L, Sa-Diniz JN, et al. Increase of O-glycosylated oncofetal fibronectin in high glucose-induced epithelial-mesenchymal transition of cultured human epithelial cells. PLoS One (2013) 8(4):e60471. doi:10.1371/journal.pone.0060471.
89. Tsai JH, Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev (2013) 27(20):2192-206. doi:10.1101/gad.225334.113.
90. Karamitopoulou E. Role of epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma: is tumor budding the missing link? Front Oncol (2013) 3:221. doi:10.3389/fonc.2013.00221.
91. Catalano V, Turdo A, Di Franco S, Dieli F, Todaro M, Stassi G. Tumor and its microenvironment: a synergistic interplay. Semin Cancer Biol (2013) 23(6 Pt B):522-32. doi:10.1016/j.semcancer.2013.08.007.
92. Creighton CJ, Gibbons DL, Kurie JM. The role of epithelial-mesenchymal transition programming in invasion and metastasis: a clinical perspective. Cancer Manag Res (2013) 5:187-95. doi:10.2147/CMAR.S35171.
93. Zeisberg M, Neilson EG. Biomarkers for epithelial-mesenchymal transitions. J Clin Invest (2009) 119(6):1429-37. doi:10.1172/JCI36183.
94. Thiery JP, Acloque H, Huang RJY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell (2009) 139(5):871-90. doi:10.1016/j.cell.2009.11.007.
95. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest (2009) 119(6):1420-8. doi:10.1172/JCI39104.
96. Klymkowsky MW, Savagner P. Epithelial-mesenchymal transition: a cancer researcher's conceptual friend and foe. Am J Pathol (2009) 174(5):1588-93. doi:10.2353/ajpath.2009.080545.
97. Guan F, Handa K, Hakomori S. Specific glycosphingolipids mediate epithelial-to-mesenchymal transition of human and mouse epithelial cell lines. Proc Natl Acad Sci U S A (2009) 106(18):7461-6. doi:10.1073/pnas.0902368106.
98. Guan F, Schaffer L, Handa K, Hakomori S. Functional role of gangliotetraosylceramide in epithelial-to-mesenchymal transition process induced by hypoxia and by TGF-beta. FASEB J (2010) 24(12):4889-903. doi:10.1096/fj.10-162107.
99. Liang YJ, Ding Y, Levery SB, Lobaton M, Handa K, Hakomori SI. Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells. Proc Natl Acad Sci U S A (2013) 110(13):4968-73. doi:10.1073/pnas.1302825110.
100. Maupin KA, Sinha A, Eugster E, Miller J, Ross J, Paulino V, et al. Glycogene expression alterations associated with pancreatic cancer epithelial-mesenchymal transition in complementary model systems. PLoS One (2010) 5(9):e13002. doi:10.1371/journal.pone.0013002.
101. Pinho SS, Oliveira P, Cabral J, Carvalho S, Huntsman D, Gartner F, et al. Loss and recovery of Mgat3 and GnT-III mediated E-cadherin N-glycosylation is a mechanism involved in epithelial-mesenchymal-epithelial transitions. PLoS One (2012) 7(3):e33191. doi:10.1371/journal.pone.0033191.
102. Lin H, Wang D, Wu T, Dong C, Shen N, Sun Y, et al. Blocking core fucosylation of TGF-beta1 receptors downregulates their functions and attenuates the epithelial-mesenchymal transition of renal tubular cells. Am J Physiol Renal Physiol (2011) 300(4):F1017-25. doi:10.1152/ajprenal.00426.2010.
103. Xu Q, Isaji T, Lu Y, Gu W, Kondo M, Fukuda T, et al. Roles of N-acetylglucosaminyltransferase III in epithelial-to-mesenchymal transition induced by transforming growth factor beta1 (TGF-beta1) in epithelial cell lines. J Biol Chem (2012) 287(20):16563-74. doi:10.1074/jbc.M111.262154.
104. Richter P, Junker K, Franz M, Berndt A, Geyer C, Gajda M, et al. IIICS de novo glycosylated fibronectin as a marker for invasiveness in urothelial carcinoma of the urinary bladder (UBC). J Cancer Res Clin Oncol (2008) 134(10):1059-65. doi:10.1007/s00432-008-0390-6.
105. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: a consensus report. Diabetes Care (2010) 33(7):1674-85. doi:10.2337/dc10-0666.
106. Shikata K, Ninomiya T, Kiyohara Y. Diabetes mellitus and cancer risk: review of the epidemiological evidence. Cancer Sci (2010) 104(1):9-14. doi:10.1111/cas.12043.
107. Peairs KS, Barone BB, Snyder CF, Yeh HC, Stein KB, Derr RL, et al. Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis. J Clin Oncol (2010) 29(1):40-6. doi:10.1200/JCO.2009.27.3011.
108. Xue F, Michels KB. Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence. Am J Clin Nutr (2007) 86(3):s823-35.
109. Currie CJ, Poole CD, Jenkins-Jones S, Gale EA, Johnson JA, Morgan CL. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care (2012) 35(2):299-304. doi:10.2337/dc11-1313.
110. Jiralerspong S, Kim ES, Dong W, Feng L, Hortobagyi GN, Giordano SH. Obesity, diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients. Ann Oncol (2013) 24(10):2506-14. doi:10.1093/annonc/mdt224.
111. Singh S, Singh PP, Singh AG, Murad MH, McWilliams RR, Chari ST. Anti-diabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Am J Gastroenterol (2013) 108(4):510-9. doi:10.1038/ajg.2013.7.
112. Onitilo AA, Engel JM, Glurich I, Stankowski RV, Williams GM, Doi SA. Diabetes and cancer II: role of diabetes medications and influence of shared risk factors. Cancer Causes Control (2012) 23(7):991-1008. doi:10.1007/s10552-012-9971-4.
113. Kim YH, Ryu JM, Lee YJ, Han HJ. Fibronectin synthesis by high glucose level mediated proliferation of mouse embryonic stem cells: involvement of ANG II and TGF-beta1. J Cell Physiol (2010) 223(2):397-407. doi:10.1002/jcp.22048.
114. Lin S, Sahai A, Chugh SS, Pan X, Wallner EI, Danesh FR, et al. High glucose stimulates synthesis of fibronectin via a novel protein kinase C, Rap1b, and B-Raf signaling pathway. J Biol Chem (2002) 277(44):41725-35. doi:10.1074/jbc.M203957200.
115. Kolm-Litty V, Sauer U, Nerlich A, Lehmann R, Schleicher ED. High glucose-induced transforming growth factor beta1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J Clin Invest (1998) 101(1):160-9. doi:10.1172/JCI119875.
116. Rocco MV, Chen Y, Goldfarb S, Ziyadeh FN. Elevated glucose stimulates TGF-beta gene expression and bioactivity in proximal tubule. Kidney Int (1992) 41(1):107-14. doi:10.1038/ki.1992.14.
117. Smoak IW. Hyperglycemia-induced TGFbeta and fibronectin expression in embryonic mouse heart. Dev Dyn (2004) 231(1):179-89. doi:10.1002/dvdy.20123.
118. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res (1997) 25(17):3389-402. doi:10.1093/nar/25.17.3389.
119. Shaw JL, Diamandis EP. Distribution of 15 human kallikreins in tissues and biological fluids. Clin Chem (2007) 53(8):1423-32. doi:10.1373/clinchem.2007.088104.
120. Kryza T, Achard C, Parent C, Marchand-Adam S, Guillon-Munos A, Iochmann S, et al. Angiogenesis stimulated by human kallikrein-related peptidase 12 acting via a platelet-derived growth factor B-dependent paracrine pathway. FASEB J (2014) 28(2):740-51. doi:10.1096/fj.13-237503.
121. Lu Z, Cui M, Zhao H, Wang T, Shen Y, Dong Q. Tissue kallikrein mediates neurite outgrowth through epidermal growth factor receptor and flotillin-2 pathway in vitro. Cell Signal (2014) 26(2):220-32. doi:10.1016/j.cellsig.2013.10.010.
122. Borgono CA, Diamandis EP. The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer (2004) 4(11):876-90. doi:10.1038/nrc1474.
123. Batra J, O'Mara T, Patnala R, Lose F, Clements JA. Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases. Biol Chem (2012) 393(12):1365-90. doi:10.1515/hsz-2012-0211.
124. Kuzmanov U, Jiang N, Smith CR, Soosaipillai A, Diamandis EP. Differential N-glycosylation of kallikrein 6 derived from ovarian cancer cells or the central nervous system. Mol Cell Proteomics (2009) 8(4):791-8. doi:10.1074/mcp.M800516-MCP200.
125. Goletz S, Hanisch FG, Karsten U. Novel alphaGalNAc containing glycans on cytokeratins are recognized invitro by galectins with type II carbohydrate recognition domains. J Cell Sci (1997) 110(Pt 14):1585-96.
126. Chou CF, Smith AJ, Omary MB. Characterization and dynamics of O-linked glycosylation of human cytokeratin 8 and 18. J Biol Chem (1992) 267(6):3901-6.
127. Hatsell S, Medina L, Merola J, Haltiwanger R, Cowin P. Plakoglobin is O-glycosylated close to the N-terminal destruction box. J Biol Chem (2003) 278(39):37745-52. doi:10.1074/jbc.M301346200.
128. Hu P, Berkowitz P, Madden VJ, Rubenstein DS. Stabilization of plakoglobin and enhanced keratinocyte cell-cell adhesion by intracellular O-glycosylation. J Biol Chem (2006) 281(18):12786-91. doi:10.1074/jbc.M511702200.
129. Lommel M, Winterhalter PR, Willer T, Dahlhoff M, Schneider MR, Bartels MF, et al. Protein O-mannosylation is crucial for E-cadherin-mediated cell adhesion. Proc Natl Acad Sci U S A (2013) 110(52):21024-9. doi:10.1073/pnas.1316753110.
130. Ha JR, Hao L, Venkateswaran G, Huang YH, Garcia E, Persad S. β-Catenin is O-GlcNAc glycosylated at serine 23: implications for beta-catenin's subcellular localization and transactivator function. Exp Cell Res (2014) 321(2):153-66. doi:10.1016/j.yexcr.2013.11.021.