Functional consequences of differential O-glycosylation of MUC1, MUC4, and MUC16 (Downstream effects on signaling)

Biomolecules

Volumn 6, Issue 3, 2016, Pages

  Hanson, Ryan L ^a   Hollingsworth, Michael A ^a  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

Cancer; MUC1; MUC16; MUC4; Mucin; O glycosylation; Signaling

Indexed keywords

EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; GALECTIN 3; GLYCOGEN SYNTHASE KINASE 3BETA; GLYCOPROTEIN; MUCIN 1; MUCIN 13; MUCIN 15; MUCIN 16; MUCIN 17; MUCIN 20; MUCIN 4; MUCIN 6; MUCIN 7; N ACETYLGALACTOSAMINE; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN P120; PROTEIN P53; SOS PROTEIN; UNCLASSIFIED DRUG; CA 125 ANTIGEN;

ENZYME ACTIVITY; HUMAN; MASS SPECTROMETRY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN GLYCOSYLATION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; TUMOR GROWTH; WNT SIGNALING PATHWAY; ANIMAL; CYTOPLASM; GLYCOSYLATION; METABOLISM; NEOPLASM;

ANIMALS; CA-125 ANTIGEN; CYTOPLASM; GLYCOSYLATION; HUMANS; MUCIN-1; MUCIN-4; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 85012108421     PISSN: None     EISSN: 2218273X     Source Type: Journal    
DOI: 10.3390/biom6030034     Document Type: Review

References (160)

1. Hollingsworth, M.A.; Swanson, B.J. Mucins in cancer: Protection and control of the cell surface. Nat. Rev. Cancer 2004, 4, 45-60. [CrossRef] [PubMed]
2. Hattrup, C.L.; Gendler, S.J. Structure and Function of the Cell Surface (Tethered) Mucins. Annu. Rev. Physiol. 2008, 70, 431-457. [CrossRef] [PubMed]
3. Thornton, D.J.; Rousseau, K.; McGuckin, M.A. Structure and Function of the Polymeric Mucins in Airways Mucus. Annu. Rev. Physiol. 2008, 70, 459-486. [CrossRef] [PubMed]
4. Argueso, P.; Gipson, I.K. Epithelial Mucins of the Ocular Surface: Structure, Biosynthesis and Function. Exp. Eye Res. 2001, 73, 281-289. [CrossRef] [PubMed]
5. Seregni, E.; Botti, C.; Massaron, S.; Lombardo, C.; Capobianco, A.; Bogni, A.; Bombardieri, E. Structure, function and gene expression of epithelial mucins. Tumori 1997, 83, 625-632. [PubMed]
6. Andrianifahanana, M.; Moniaux, N.; Batra, S.K. Regulation of mucin expression: Mechanistic aspects and implications for cancer and inflammatory diseases. Biochim. Biophys. Acta 2006, 1765, 189-222. [CrossRef] [PubMed]
7. Voynow, J.A.; Gendler, S.J.; Rose, M.C. Regulation of mucin genes in chronic inflammatory airway diseases. Am. J. Respir. Cell Mol. Biol. 2006, 34, 661-665. [CrossRef] [PubMed]
8. Singh, P.K.; Hollingsworth, M.A. Cell surface-associated mucins in signal transduction. Trends Cell Biol. 2006, 16, 467-476. [CrossRef] [PubMed]
9. Timpte, C.S.; Eckhardt, A.E.; Abernethy, J.L.; Hill, R.L. Porcine submaxillary gland apomucin contains tandemly repeated, identical sequences of 81 residues. J. Biol. Chem. 1988, 263, 1081-1088. [PubMed]
10. Gupta, R.; Jentoft, N. Subunit structure of porcine submaxillary mucin. Biochemistry 1989, 28, 6114-6121. [CrossRef] [PubMed]
11. Carlstedt, I.; Sheehan, J.K.; Corfield, A.P.; Gallagher, J.T. Mucous glycoproteins: A gel of a problem. Essays Biochem. 1985, 20, 40-76. [PubMed]
12. McDermott, K.M.; Crocker, P.R.; Harris, A.; Burdick, M.D.; Hinoda, Y.; Hayashi, T.; Imai, K.; Hollingsworth, M.A. Overexpression of MUC1 reconfigures the binding properties of tumor cells. Int. J. Cancer 2001, 94, 783-791. [CrossRef] [PubMed]
13. Bennett, E.P.; Mandel, U.; Clausen, H.; Gerken, T.A.; Fritz, T.A.; Tabak, L.A. Control of mucin-type O-glycosylation: A classification of the polypeptide GalNAc-transferase gene family. Glycobiology 2012, 22, 736-756. [CrossRef] [PubMed]
14. Carraway, K.L.; Hull, S.R. O-glycosylation pathway for mucin-type glycoproteins. BioEssays 1989, 10, 117-121. [CrossRef] [PubMed]
15. Hanisch, F.G. O-Glycosylation of the Mucin Type. Biol. Chem. 2001, 382, 143-149. [CrossRef] [PubMed]
16. Jensen, P.H.; Kolarich, D.; Packer, N.H. Mucin-type O-glycosylation-putting the pieces together. FEBS J. 2010, 277, 81-94. [CrossRef] [PubMed]
17. Clausen, H.; Bennett, E.P. A family of UDP-GalNAc: Polypeptide N-acetylgalactosaminyl-transferases control the initiation of mucin-type O-linked glycosylation. Glycobiology 1996, 6, 635-646. [CrossRef] [PubMed]
18. Cheng, P.W.; Radhakrishnan, P. Mucin O-Glycan Branching Enzymes: structure, Function, and Gene Regulation. Adv. Exp. Med. Biol. 2011, 705, 465-492. [PubMed]
19. Ju, T.; Brewer, K.; D’Souza, A.; Cummings, R.D.; Canfield,W.M. Cloning and Expression of Human Core 1β1,3-Galactosyltransferase. J. Biol. Chem. 2002, 277, 178-186. [CrossRef] [PubMed]
20. Bierhuizen, M.F.; Fukuda, M. Expression cloning of a cDNA encoding UDP-GlcNAc:Galβ1-3-GalNAc-R (GlcNAc to GalNAc) β1-6GlcNAc transferase by gene transfer into CHO cells expressing polyoma large tumor antigen. Proc. Natl. Acad. Sci. USA 1992, 89, 9326-9330. [CrossRef] [PubMed]
21. Schwientek, T.; Nomoto, M.; Levery, S.B.; Merkx, G.; van Kessel, A.G.; Bennett, E.P.; Hollingsworth, M.A.; Clausen, H. Control of O-Glycan Branch Formation. Molecular Cloning of Human cDNA Encoding a Novel β1,6-N-Acetylglucosaminyltransferase Forming Core 2 and Core 4. J. Biol. Chem. 1999, 274, 4504-4512. [CrossRef] [PubMed]
22. Tarp, M.A.; Clausen, H. Mucin-type O-glycosylation and its potential use in drug and vaccine development. Biochim. Biophys. Acta 2008, 1780, 546-563. [CrossRef] [PubMed]
23. Iwai, T.; Inaba, N.; Naundorf, A.; Zhang, Y.; Gotoh, M.; Iwasaki, H.; Kudo, T.; Togayachi, A.; Ishizuka, Y.; Nakanishi, H.; et al. Molecular Cloning and Characterization of a Novel UDP-GlcNAc:GalNAc-peptide β1,3-N-acetylglucosaminyltransferase (β3Gn-T6), an Enzyme Synthesizing the Core 3 Structure of O-Glycans. J. Biol. Chem. 2002, 277, 12802-12809. [CrossRef] [PubMed]
24. Krishn, S.R.; Kaur, S.; Smith, L.M.; Johansson, S.L.; Jain, M.; Patel, A.; Gautam, S.K.; Hollingsworth, M.A.; Mandel, U.; Clausen, H.; et al. Mucins and associated glycan signatures in colon adenoma-carcinoma sequence: Prospective pathological implication(s) for early diagnosis of colon cancer. Cancer Lett. 2016, 374, 304-314. [CrossRef] [PubMed]
25. Gendler, S.J. MUC1, The Renaissance Molecule. J. Mammary Gland Biol. Neoplasia 2001, 6, 339-353. [CrossRef] [PubMed]
26. Awaya, H.; Takeshima, Y.; Yamasaki, M.; Inai, K. Expression of MUC1, MUC2, MUC5AC, and MUC6 in Atypical Adenomatous Hyperplasia, Bronchioloalveolar Carcinoma, AdenocarcinomaWith Mixed Subtypes, and Mucinous Bronchioloalveolar Carcinoma of the Lung. Am. J. Clin. Pathol. 2004, 121, 644-653. [CrossRef] [PubMed]
27. Singh, A.P.; Chauhan, S.C.; Bafna, S.; Johansson, S.L.; Smith, L.M.; Moniaux, N.; Lin, M.F.; Batra, S.K. Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas. Prostate 2006, 66, 421-429. [CrossRef] [PubMed]
28. Andrianifahanana, M.; Moniaux, N.; Schmied, B.M.; Ringel, J.; Friess, H.; Hollingsworth, M.A.; Buchler, M.W.; Aubert, J.P.; Batra, S.K. Mucin (MUC) Gene Expression in Human Pancreatic Adenocarcinoma and Chronic Pancreatitis: A potential role of MUC4 as a tumor marker of diagnostic significance. Clin. Cancer Res. 2001, 7, 4033-4040. [PubMed]
29. Schwartz, P.E.; Chambers, S.K.; Chambers, J.T.; Gutmann, J.; Katopodis, N.; Foemmel, R. Circulating Tumor Markers in the Monitoring of Gynecologic Malignancies. Cancer 1987, 60, 353-361. [CrossRef]
30. Yin, B.W.; Dnistrian, A.; Lloyd, K.O. Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene. Int. J. Cancer 2002, 98, 737-740. [CrossRef] [PubMed]
31. Higashi, M.; Yokoyama, S.; Yamamoto, T.; Goto, Y.; Kitazono, I.; Hiraki, T.; Taguchi, H.; Hashimoto, S.; Fukukura, Y.; Koriyama, C.; et al. Mucin Expression in Endoscopic Ultrasound-Guided Fine-Needle Aspiration Specimens Is a Useful Prognostic Factor in Pancreatic Ductal Adenocarcinoma. Pancreas 2015, 44, 728-734. [CrossRef] [PubMed]
32. Haridas, D.; Chakraborty, S.; Ponnusamy, M.P.; Lakshmanan, I.; Rachagani, S.; Cruz, E.; Kumar, S.; Das, S.; Lele, S.M.; Anderson, J.M.; et al. Pathobiological Implications of MUC16 Expression in Pancreatic Cancer. PLoS ONE 2011, 6, e26839. [CrossRef] [PubMed]
33. Remmers, N.; Anderson, J.M.; Linde, E.M.; DiMaio, D.J.; Lazenby, A.J.; Wandall, H.H.; Mandel, U.; Clausen, H.; Yu, F.; Hollingsworth, M.A. Aberrant Expression of Mucin Core Proteins and O-Linked Glycans Associated with Progression of Pancreatic Cancer. Clin. Cancer Res. 2013, 19, 1981-1993. [CrossRef] [PubMed]
34. Hinoda, Y.; Ikematsu, Y.; Horinochi, M.; Sato, S.; Yamamoto, K.; Nakano, T.; Fukui, M.; Suehiro, Y.; Hamanaka, Y.; Nishikawa, Y.; et al. Increased expression of MUC1 in advanced pancreatic cancer. J. Gastroenterol. 2003, 38, 1162-1166. [CrossRef] [PubMed]
35. Huang, X.; Wang, X.; Lu, S.M.; Chen, C.; Wang, J.; Zheng, Y.Y.; Ren, B.H.; Xu, L. Clinicopathological and prognostic significance of MUC4 expression in cancers: Evidence from meta-analysis. Int. J. Clin. Exp. Med. 2015, 8, 10274-10283. [PubMed]
36. Ghosh, S.K.; Pantazopoulos, P.; Medarova, Z.; Moore, A. Expression of Underglycosylated MUC1 Antigen in Cancerous and Adjacent Normal Breast Tissues. Clin. Breast Cancer 2013, 13, 109-118. [CrossRef] [PubMed]
37. Rakha, E.A.; Boyce, R.W.; Abd El-Rehim, D.; Kurien, T.; Green, A.R.; Paish, E.C.; Robertson, J.F.; Ellis, I.O. Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod. Pathol. 2005, 18, 1295-1304. [CrossRef] [PubMed]
38. Mukhopadhyay, P.; Chakraborty, S.; Ponnusamy, M.P.; Lakshmanan, I.; Jain, M.; Batra, S.K. Mucins in the pathogenesis of breast cancer: Implications in diagnosis, prognosis and therapy. Biochim. Biophys. Acta 2011, 1815, 224-240. [CrossRef] [PubMed]
39. Terada, T. An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: II. Expression of MUC1, MUC2, MUC5AC, and MUC6 in normal mucosa and in 42 cases. Int. J. Clin. Exp. Pathol. 2013, 6, 613-621. [PubMed]
40. Kwon, K.Y.; Ro, J.Y.; Singhal, N.; Killen, D.E.; Sienko, A.; Allen, T.C.; Zander, D.S.; Barrios, R.; Haque, A.; Cagle, P.T. MUC4 Expression in Non-Small Cell Lung Carcinomas: Relationship to Tumor Histology and Patient Survival. Arch. Pathol. Lab. Med. 2007, 131, 593-598. [PubMed]
41. Yin, B.W.; Lloyd, K.O. Molecular Cloning of the CA125 Ovarian Cancer Antigen: Identification as a New Mucin, MUC16. J. Biol. Chem. 2001, 276, 27371-27375. [CrossRef] [PubMed]
42. Chauhan, S.C.; Singh, A.P.; Ruiz, F.; Johansson, S.L.; Jain, M.; Smith, L.M.; Moniaux, N.; Batra, S.K. Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125). Mod. Pathol. 2006, 19, 1386-1394. [CrossRef] [PubMed]
43. Osunkoya, A.O.; Adsay, N.V.; Cohen, C.; Epstein, J.I.; Smith, S.L. MUC2 expression in primary mucinous and nonmucinous adenocarcinoma of the prostate: An analysis of 50 cases on radical prostatectomy. Mod. Pathol. 2008, 21, 789-794. [CrossRef] [PubMed]
44. Hakomori, S. Aberrant Glycosylation in Cancer Cell Membranes as Focused on Glycolipids: Overview and Perspectives. Cancer Res. 1985, 45, 2405-2414. [PubMed]
45. Springer, G.F. T and Tn, general carcinoma autoantigens. Science 1984, 224, 1198-1206. [CrossRef] [PubMed]
46. Ju, T.; Lanneau, G.S.; Gautam, T.; Wang, Y.; Xia, B.; Stowell, S.R.; Willard, M.T.; Wang, W.; Xia, J.Y.; Zuna, R.E.; et al. Human Tumor Antigens Tn and Sialyl Tn Arise from Mutations in Cosmc. Cancer Res. 2008, 68, 1636-1646. [CrossRef] [PubMed]
47. Ju, T.; Cummings, R.D. A unique molecular chaperone Cosmc required for activity of the mammalian core 1β3-galactosyltransferase. Proc. Natl. Acad. Sci. USA 2002, 99, 16613-16618. [CrossRef] [PubMed]
48. Ju, T.; Aryal, R.P.; Stowell, C.J.; Cummings, R.D. Regulation of protein O-glycosylation by the endoplasmic reticulum-localized molecular chaperone Cosmc. J. Cell Biol. 2008, 182, 531-542. [CrossRef] [PubMed]
49. Sun, Q.; Ju, T.; Cummings, R.D. The Transmembrane Domain of the Molecular Chaperone Cosmc Directs Its Localization to the Endoplasmic Reticulum. J. Biol. Chem. 2011, 286, 11529-11542. [CrossRef] [PubMed]
50. Yu, X.; Du, Z.; Sun, X.; Shi, C.; Zhang, H.; Hu, T. Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29. Int. J. Clin. Exp. Pathol. 2015, 8, 2590-2602. [PubMed]
51. Hofmann, B.T.; Schluter, L.; Lange, P.; Mercanoglu, B.; Ewald, F.; Folster, A.; Picksak, A.S.; Harder, S.; El Gammal, A.T.; Grupp, K.; et al. Cosmc knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer. Mol. Cancer 2015, 14, 109. [CrossRef] [PubMed]
52. Radhakrishnan, P.; Dabelsteen, S.; Madsen, F.B.; Francavilla, C.; Kopp, K.L.; Steentoft, C.; Vakhrushev, S.Y.; Olsen, J.V.; Hansen, L.; Bennett, E.P.; et al. Immature truncated O-glycophenotype of cancer directly induces oncogenic features. Proc. Natl. Acad. Sci. USA 2014, 111, E4066-4075. [CrossRef] [PubMed]
53. Mi, R.; Song, L.;Wang, Y.; Ding, X.; Zeng, J.; Lehoux, S.; Aryal, R.P.;Wang, J.; Crew, V.K.; van Die, I.; et al. Epigenetic Silencing of the Chaperone Cosmc in Human Leukocytes Expressing Tn Antigen. J. Biol. Chem. 2012, 287, 41523-41533. [CrossRef] [PubMed]
54. Schneider, F.; Kemmner, W.; Haensch, W.; Franke, G.; Gretschel, S.; Karsten, U.; Schlag, P.M. Overexpression of Sialyltransferase CMP-Sialic Acid:Galβ1,3GalNAc-R α6-Sialyltransferase Is Related to Poor Patient sSurvival in Human Colorectal Carcinomas. Cancer Res. 2001, 61, 4605-4611. [PubMed]
55. Georgopoulou, N.; Breen, K.C. Overexpression of α2,3 sialyltransferase in neuroblastoma cells results in an upset in the glycosylation process. Glycoconj. J. 1999, 16, 649-657. [CrossRef] [PubMed]
56. Brockhausen, I.; Yang, J.M.; Burchell, J.; Whitehouse, C.; Taylor-Papadimitriou, J. Mechanisms Underlying Aberrant Glycosylation of MUC1 Mucin in Breast Cancer Cells. Eur. J. Biochem. 1995, 233, 607-617. [CrossRef] [PubMed]
57. Ogawa, J.; Inoue, H.; Koide, S. Expression of α-1,3-Fucosyltransferase Type IV and VII Genes Is Related to Poor Prognosis in Lung Cancer. Cancer Res. 1996, 56, 325-329. [PubMed]
58. Barthel, S.R.;Wiese, G.K.; Cho, J.; Opperman, M.J.; Hays, D.L.; Siddiqui, J.; Pienta, K.J.; Furie, B.; Dimitroff, C.J. Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking. Proc. Natl. Acad. Sci. USA 2009, 106, 19491-19496. [CrossRef] [PubMed]
59. Hauselmann, I.; Borsig, L. Altered tumor-cell glycosylation promotes metastasis. Front. Oncol. 2014, 4, 28. [CrossRef] [PubMed]
60. Iwai, T.; Kudo, T.; Kawamoto, R.; Kubota, T.; Togayachi, A.; Hiruma, T.; Okada, T.; Kawamoto, T.; Morozumi, K.; Narimatsu, H. Core 3 synthase is down-regulated in colon carcinoma and profoundly suppresses the metastatic potential of carcinoma cells. Proc. Natl. Acad. Sci. USA 2005, 102, 4572-4577. [CrossRef] [PubMed]
61. Huang, M.C.; Chen, H.Y.; Huang, H.C.; Huang, J.; Liang, J.T.; Shen, T.L.; Lin, N.Y.; Ho, C.C.; Cho, I.M.; Hsu, S.M. C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells. Oncogene 2006, 25, 3267-3276. [CrossRef] [PubMed]
62. Gill, D.J.; Chia, J.; Senewiratne, J.; Bard, F. Regulation of O-glycosylation through Golgi-to-ER relocation of initiation enzymes. J. Cell Biol. 2010, 189, 843-858. [CrossRef] [PubMed]
63. Gill, D.J.; Clausen, H.; Bard, F. Location, location, location: New insights into O-GalNAc protein glycosylation. Trends Cell Biol. 2011, 21, 149-158. [CrossRef] [PubMed]
64. Muller, S.; Alving, K.; Peter-Katalinic, J.; Zachara, N.; Gooley, A.A.; Hanisch, F.G. High Density O-Glycosylation on Tandem Repeat Peptide from Secretory MUC1 of T47D Breast Cancer Cells. J. Biol. Chem. 1999, 274, 18165-18172. [CrossRef] [PubMed]
65. Springer, G.F. Tn epitope (N-acetyl-D-galactosamine α-O-serine/threonine) density in primary breast carcinoma: A functional predictor of aggressiveness. Mol. Immunol. 1989, 26, 1-5. [CrossRef]
66. Gerken, T.A.; Owens, C.L.; Pasumarthy, M. Site-specific Core 1 O-Glycosylation Pattern of the Porcine Submaxillary Gland Mucin Tandem Repeat. Evidence for The Modulation of Glycan Length by Peptide Sequence. J. Biol. Chem. 1998, 273, 26580-26588. [CrossRef] [PubMed]
67. Yeatman, T.J. A renaissance for SRC. Nat. Rev. Cancer 2004, 4, 470-480. [CrossRef] [PubMed]
68. Hasemann, C.A.; Capra, J.D. High-level production of a functional immunoglobulin heterodimer in a baculovirus expression system. Proc. Natl. Acad. Sci. USA 1990, 87, 3942-3946. [CrossRef] [PubMed]
69. Frenzel, A.; Hust, M.; Schirrmann, T. Expression of recombinant antibodies. Front. Immunol. 2013, 4, 217. [CrossRef] [PubMed]
70. Radhakrishnan, P.; Grandgenett, P.M.; Mohr, A.M.; Bunt, S.K.; Yu, F.; Chowdhury, S.; Hollingsworth, M.A. Expression of core 3 synthase in human pancreatic cancer cells suppresses tumor growth and metastasis. Int. J. Cancer 2013, 133, 2824-2833. [CrossRef] [PubMed]
71. Macao, B.; Johansson, D.G.; Hansson, G.C.; Hard, T. Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin. Nat. Struct. Mol. Biol. 2006, 13, 71-76. [CrossRef] [PubMed]
72. Levitin, F.; Stern, O.;Weiss, M.; Gil-Henn, C.; Ziv, R.; Prokocimer, Z.; Smorodinsky, N.I.; Rubinstein, D.B.; Wreschner, D.H. The MUC1 SEA Module Is a Self-cleaving Domain. J. Biol. Chem. 2005, 280, 33374-33386. [CrossRef] [PubMed]
73. Palmai-Pallag, T.; Khodabukus, N.; Kinarsky, L.; Leir, S.H.; Sherman, S.; Hollingsworth, M.A.; Harris, A. The role of the SEA (sea urchin sperm protein, enterokinase and agrin) module in cleavage of membrane-tethered mucins. FEBS J. 2005, 272, 2901-2911. [CrossRef] [PubMed]
74. Singh, P.K.; Behrens, M.E.; Eggers, J.P.; Cerny, R.L.; Bailey, J.M.; Shanmugam, K.; Gendler, S.J.; Bennett, E.P.; Hollingsworth, M.A. Phosphorylation of MUC1 by Met Modulates Interaction with p53 and MMP1 Expression. J. Biol. Chem. 2008, 283, 26985-26995. [CrossRef] [PubMed]
75. Behrens, M.E.; Grandgenett, P.M.; Bailey, J.M.; Singh, P.K.; Yi, C.H.; Yu, F.; Hollingsworth, M.A. The reactive tumor microenvironment: MUC1 signaling directly reprograms transcription of CTGF. Oncogene 2010, 29, 5667-5677. [CrossRef] [PubMed]
76. Schroeder, J.A.; Thompson, M.C.; Gardner, M.M.; Gendler, S.J. Transgenic MUC1 Interacts with Epidermal Growth Factor Receptor and Correlates with Mitogen-activated Protein Kinase Activation in the Mouse Mammary Gland. J. Biol. Chem. 2001, 276, 13057-13064. [CrossRef] [PubMed]
77. Singh, P.K.; Wen, Y.; Swanson, B.J.; Shanmugam, K.; Kazlauskas, A.; Cerny, R.L.; Gendler, S.J.; Hollingsworth, M.A. Platelet-Derived Growth Factor Receptor β-Mediated Phosphorylation of MUC1 Enhances Invasiveness in Pancreatic Adenocarcinoma Cells. Cancer Res. 2007, 67, 5201-5210. [CrossRef] [PubMed]
78. Li, Y.; Bharti, A.; Chen, D.; Gong, J.; Kufe, D. Interaction of Glycogen Synthase Kinase 3β with the DF3/MUC1 Carcinoma-Associated Antigen and β-Catenin. Mol. Cell. Biol. 1998, 18, 7216-7224. [CrossRef] [PubMed]
79. Mertins, P.; Yang, F.; Liu, T.; Mani, D.R.; Petyuk, V.A.; Gillette, M.A.; Clauser, K.R.; Qiao, J.W.; Gritsenko, M.A.; Moore, R.J.; et al. Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol. Cell. Proteom. 2014, 13, 1690-1704. [CrossRef] [PubMed]
80. Rikova, K.; Guo, A.; Zeng, Q.; Possemato, A.; Yu, J.; Haack, H.; Nardone, J.; Lee, K.; Reeves, C.; Li, Y.; et al. Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer. Cell 2007, 131, 1190-1203. [CrossRef] [PubMed]
81. Gu, T.L.; Deng, X.; Huang, F.; Tucker, M.; Crosby, K.; Rimkunas, V.; Wang, Y.; Deng, G.; Zhu, L.; Tan, Z.; et al. Survey of Tyrosine Kinase Signaling Reveals ROS Kinase Fusions in Human Cholangiocarcinoma. PLoS ONE 2011, 6, e15640. [CrossRef] [PubMed]
82. Pandey, P.; Kharbanda, S.; Kufe, D. Association of the DF3/MUC1 Breast Cancer Antigen with Grb2 and the Sos/Ras Exchange Protein. Cancer Res. 1995, 55, 4000-4003. [PubMed]
83. Meerzaman, D.; Shapiro, P.S.; Kim, K.C. Involvement of the MAP kinase ERK2 in MUC1 mucin signaling. Am. J. Physiol. Lung Cell. Mol. Physiol. 2001, 281, L86-91. [PubMed]
84. Trehoux, S.; Duchene, B.; Jonckheere, N.; Van Seuningen, I. The MUC1 oncomucin regulates pancreatic cancer cell biological properties and chemoresistance. Implication of p42-44 MAPK, Akt, Bcl-2 and MMP13 pathways. Biochem. Biophys. Res. Commun. 2015, 456, 757-762. [CrossRef] [PubMed]
85. Hanson, R.L.; Brown, R.B.; Steele, M.M.; Grandgenett, P.M.; Grunkemeyer, J.A.; Hollingsworth, M.A. Identification of FRA1 as a novel player in pancreatic cancer in cooperation with a MUC1: ERK signaling axis. Oncotarget 2016. [CrossRef] [PubMed]
86. Bitler, B.G.; Goverdhan, A.; Schroeder, J.A. MUC1 regulates nuclear localization and function of the epidermal growth factor receptor. J. Cell Sci. 2010, 123, 1716-1723. [CrossRef] [PubMed]
87. Wei, X.; Xu, H.; Kufe, D. Human MUC1 oncoprotein regulates p53-responsive gene transcription in the genotoxic stress response. Cancer Cell 2005, 7, 167-178. [CrossRef] [PubMed]
88. Liu, X.; Caffrey, T.C.; Steele, M.M.; Mohr, A.; Singh, P.K.; Radhakrishnan, P.; Kelly, D.L.; Wen, Y.; Hollingsworth, M.A. MUC1 regulates cyclin D1 gene expression through p120 catenin and β-catenin. Oncogenesis 2014, 3, e107. [CrossRef] [PubMed]
89. Li, Y.; Kufe, D. The Human DF3/MUC1 Carcinoma-Associated Antigen Signals Nuclear Localization of the Catenin p120ctn. Biochem. Biophys. Res. Commun. 2001, 281, 440-443. [CrossRef] [PubMed]
90. Liu, X.; Yi, C.; Wen, Y.; Radhakrishnan, P.; Tremayne, J.R.; Dao, T.; Johnson, K.R.; Hollingsworth, M.A. Interactions between MUC1 and p120 catenin regulate dynamic features of cell adhesion, motility, and metastasis. Cancer Res. 2014, 74, 1609-1620. [CrossRef] [PubMed]
91. Kinlough, C.L.; Poland, P.A.; Bruns, J.B.; Harkleroad, K.L.; Hughey, R.P. MUC1 Membrane Trafficking Is Modulated by Multiple Interactions. J. Biol. Chem. 2004, 279, 53071-53077. [CrossRef] [PubMed]
92. Kinlough, C.L.; McMahan, R.J.; Poland, P.A.; Bruns, J.B.; Harkleroad, K.L.; Stremple, R.J.; Kashlan, O.B.; Weixel, K.M.;Weisz, O.A.; Hughey, R.P. Recycling of MUC1 Is Dependent on Its Palmitoylation. J. Biol. Chem. 2006, 281, 12112-12122. [CrossRef] [PubMed]
93. Kato, K.; Lu, W.; Kai, H.; Kim, K.C. Phosphoinositide 3-kinase is activated by MUC1 but not responsible for MUC1-induced suppression of Toll-like receptor 5 signaling. Am. J. Physiol. Lung Cell. Mol. Physiol. 2007, 293, L686-692. [CrossRef] [PubMed]
94. Ren, J.; Li, Y.; Kufe, D. Protein Kinase C δ Regulates Function of the DF3/MUC1 Carcinoma Antigen in β-Catenin Signaling. J. Biol. Chem. 2002, 277, 17616-17622. [CrossRef] [PubMed]
95. Li, Y.; Kuwahara, H.; Ren, J.; Wen, G.; Kufe, D. The c-Src Tyrosine Kinase Regulates Signaling of the Human DF3/MUC1 Carcinoma-Associated Antigen with GSK3β and β-Catenin. J. Biol. Chem. 2001, 276, 6061-6064. [CrossRef] [PubMed]
96. Das, S.; Majhi, P.D.; Al-Mugotir, M.H.; Rachagani, S.; Sorgen, P.; Batra, S.K. Membrane proximal ectodomain cleavage of MUC16 occurs in the acidifying Golgi/post-Golgi compartments. Sci. Rep. 2015, 5, 9759. [CrossRef] [PubMed]
97. Akita, K.; Tanaka, M.; Tanida, S.; Mori, Y.; Toda, M.; Nakada, H. CA125/MUC16 interacts with Src family kinases, and over-expression of its C-terminal fragment in human epithelial cancer cells reduces cell-cell adhesion. Eur. J. Cell Biol. 2013, 92, 257-263. [CrossRef] [PubMed]
98. Song, K.; Herzog, B.H.; Fu, J.; Sheng, M.; Bergstrom, K.; McDaniel, J.M.; Kondo, Y.; McGee, S.; Cai, X.; Li, P.; et al. Loss of Core 1-derived O-Glycans Decreases Breast Cancer Development in Mice. J. Biol. Chem. 2015, 290, 20159-20166. [CrossRef] [PubMed]
99. Chou, C.H.; Huang, M.J.; Chen, C.H.; Shyu, M.K.; Huang, J.; Hung, J.S.; Huang, C.S.; Huang, M.C. Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway. Oncotarget 2015, 6, 6123-6135. [CrossRef] [PubMed]
100. Solatycka, A.; Owczarek, T.; Piller, F.; Piller, V.; Pula, B.;Wojciech, L.; Podhorska-Okolow, M.; Dziegiel, P.; Ugorski, M. MUC1 in human and murine mammary carcinoma cells decreases the expression of core 2β1,6-N-acetylglucosaminyltransferase and β-galactoside α2,3-sialyltransferase. Glycobiology 2012, 22, 1042-1054. [CrossRef] [PubMed]
101. Cascio, S.; Farkas, A.M.; Hughey, R.P.; Finn, O.J. Altered glycosylation of MUC1 influences its association with CIN85: the role of this novel complex in cancer cell invasion and migration. Oncotarget 2013, 4, 1686-1697. [CrossRef] [PubMed]
102. Kowanetz, K.; Szymkiewicz, I.; Haglund, K.; Kowanetz, M.; Husnjak, K.; Taylor, J.D.; Soubeyran, P.; Engstrom, U.; Ladbury, J.E.; Dikic, I. Identification of a Novel Proline-Arginine Motif Involved in CIN85-dependent Clustering of Cbl and Down-regulation of Epidermal Growth Factor Receptors. J. Biol. Chem. 2003, 278, 39735-39746. [CrossRef] [PubMed]
103. Kowanetz, K.; Husnjak, K.; Holler, D.; Kowanetz, M.; Soubeyran, P.; Hirsch, D.; Schmidt, M.H.; Pavelic, K.; De Camilli, P.; Randazzo, P.A.; et al. CIN85 Associates with Multiple Effectors Controlling Intracellular Trafficking of Epidermal Growth Factor Receptors. Mol. Biol. Cell 2004, 15, 3155-3166. [CrossRef] [PubMed]
104. Kufe, D.W. MUC1-C oncoprotein as a target in breast cancer: Activation of signaling pathways and therapeutic approaches. Oncogene 2013, 32, 1073-1081. [CrossRef] [PubMed]
105. Kharbanda, A.; Rajabi, H.; Jin, C.; Tchaicha, J.; Kikuchi, E.; Wong, K.K.; Kufe, D. Targeting the oncogenic MUC1-C protein inhibits mutant EGFR-mediated signaling and survival in non-small cell lung cancer cells. Clin. Cancer Res. 2014, 20, 5423-5434. [CrossRef] [PubMed]
106. Li, Q.; Liu, G.; Yuan, H.;Wang, J.; Guo, Y.; Chen, T.; Zhai, R.; Shao, D.; Ni,W.; Tai, G. Mucin1 shifts Smad3 signaling from the tumor-suppressive pSmad3C/p21WAF1 pathway to the oncogenic pSmad3L/c-Myc pathway by activating JNK in human hepatocellular carcinoma cells. Oncotarget 2015, 6, 4253-4265. [CrossRef] [PubMed]
107. Wang, J.; Liu, G.; Li, Q.;Wang, F.; Xie, F.; Zhai, R.; Guo, Y.; Chen, T.; Zhang, N.; Ni,W.; et al. Mucin1 promotes the migration and invasion of hepatocellular carcinoma cells via JNK-mediated phosphorylation of Smad2 at the C-terminal and linker regions. Oncotarget 2015, 6, 19264-19278. [CrossRef] [PubMed]
108. Merlin, J.; Stechly, L.; de Beauce, S.; Monte, D.; Leteurtre, E.; van Seuningen, I.; Huet, G.; Pigny, P. Galectin-3 regulates MUC1 and EGFR cellular distribution and EGFR downstream pathways in pancreatic cancer cells. Oncogene 2011, 30, 2514-2525. [CrossRef] [PubMed]
109. De Oliveira, J.T.; de Matos, A.J.; Santos, A.L.; Pinto, R.; Gomes, J.; Hespanhol, V.; Chammas, R.; Manninen, A.; Bernardes, E.S.; Albuquerque Reis, C.; et al. Sialylation regulates galectin-3/ligand interplay during mammary tumour progression - a case of targeted uncloaking. Int. J. Dev. Biol. 2011, 55, 823-834. [CrossRef] [PubMed]
110. Rodriguez, M.C.; Yegorova, S.; Pitteloud, J.P.; Chavaroche, A.E.; Andre, S.; Arda, A.; Minond, D.; Jimenez-Barbero, J.; Gabius, H.J.; Cudic, M. Thermodynamic Switch in Binding of Adhesion/Growth Regulatory Human Galectin-3 to Tumor-Associated TF Antigen (CD176) and MUC1 Glycopeptides. Biochemistry 2015, 54, 4462-4474. [CrossRef] [PubMed]
111. Yu, L.G.; Andrews, N.; Zhao, Q.; McKean, D.; Williams, J.F.; Connor, L.J.; Gerasimenko, O.V.; Hilkens, J.; Hirabayashi, J.; Kasai, K.; et al. Galectin-3 Interaction with Thomsen-Friedenreich Disaccharide on Cancer-associated MUC1 Causes Increased Cancer Cell Endothelial Adhesion. J. Biol. Chem. 2007, 282, 773-781. [CrossRef] [PubMed]
112. Zhao, Q.; Guo, X.; Nash, G.B.; Stone, P.C.; Hilkens, J.; Rhodes, J.M.; Yu, L.G. Circulating Galectin-3 Promotes Metastasis by Modifying MUC1 Localization on Cancer Cell Surface. Cancer Res. 2009, 69, 6799-6806. [CrossRef] [PubMed]
113. Zhao, Q.; Barclay, M.; Hilkens, J.; Guo, X.; Barrow, H.; Rhodes, J.M.; Yu, L.G. Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis. Mol. Cancer 2010, 9, 154. [CrossRef] [PubMed]
114. Altschuler, Y.; Kinlough, C.L.; Poland, P.A.; Bruns, J.B.; Apodaca, G.; Weisz, O.A.; Hughey, R.P. Clathrin-mediated Endocytosis of MUC1 Is Modulated by Its Glycosylation State. Mol. Biol. Cell 2000, 11, 819-831. [CrossRef] [PubMed]
115. Kufe, D.W. Functional targeting of the MUC1 oncogene in human cancers. Cancer Biol. Ther. 2009, 8, 1197-1203. [CrossRef] [PubMed]
116. Duraisamy, S.; Ramasamy, S.; Kharbanda, S.; Kufe, D. Distinct evolution of the human carcinoma-associated transmembrane mucins, MUC1, MUC4 and MUC16. Gene 2006, 373, 28-34. [CrossRef] [PubMed]
117. Escande, F.; Lemaitre, L.; Moniaux, N.; Batra, S.K.; Aubert, J.P.; Buisine, M.P. Genomic organization of MUC4 mucin gene. Towards the characterization of splice variants. Eur. J. Biochem. 2002, 269, 3637-3644. [CrossRef] [PubMed]
118. Chaturvedi, P.; Singh, A.P.; Batra, S.K. Structure, evolution, and biology of the MUC4 mucin. FASEB J. 2008, 22, 966-981. [CrossRef] [PubMed]
119. Ponnusamy, M.P.; Singh, A.P.; Jain, M.; Chakraborty, S.; Moniaux, N.; Batra, S.K. MUC4 activates HER2 signalling and enhances the motility of human ovarian cancer cells. Br. J. Cancer 2008, 99, 520-526. [CrossRef] [PubMed]
120. Mukhopadhyay, P.; Lakshmanan, I.; Ponnusamy, M.P.; Chakraborty, S.; Jain, M.; Pai, P.; Smith, L.M.; Lele, S.M.; Batra, S.K. MUC4 Overexpression Augments Cell Migration and Metastasis through EGFR Family Proteins in Triple Negative Breast Cancer Cells. PLoS ONE 2013, 8, e54455. [CrossRef] [PubMed]
121. Lakshmanan, I.; Seshacharyulu, P.; Haridas, D.; Rachagani, S.; Gupta, S.; Joshi, S.; Guda, C.; Yan, Y.; Jain, M.; Ganti, A.K.; et al. Novel HER3/MUC4 oncogenic signaling aggravates the tumorigenic phenotypes of pancreatic cancer cells. Oncotarget 2015, 6, 21085-21099. [CrossRef] [PubMed]
122. Ponnusamy, M.P.; Seshacharyulu, P.; Vaz, A.; Dey, P.; Batra, S.K. MUC4 stabilizes HER2 expression and maintains the cancer stem cell population in ovarian cancer cells. J. Ovarian Res. 2011, 4, 7. [CrossRef] [PubMed]
123. Chaturvedi, P.; Singh, A.P.; Chakraborty, S.; Chauhan, S.C.; Bafna, S.; Meza, J.L.; Singh, P.K.; Hollingsworth, M.A.; Mehta, P.P.; Batra, S.K. MUC4 Mucin Interacts with and Stabilizes the HER2 Oncoprotein in Human Pancreatic Cancer Cells. Cancer Res. 2008, 68, 2065-2070. [CrossRef] [PubMed]
124. Jonckheere, N.; Perrais, M.; Mariette, C.; Batra, S.K.; Aubert, J.P.; Pigny, P.; Van Seuningen, I. A role for human MUC4 mucin gene, the ErbB2 ligand, as a target of TGF-β in pancreatic carcinogenesis. Oncogene 2004, 23, 5729-5738. [CrossRef] [PubMed]
125. Jepson, S.; Komatsu, M.; Haq, B.; Arango, M.E.; Huang, D.; Carraway, C.A.; Carraway, K.L. MUC4/ sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinase B/Akt pathways. Oncogene 2002, 21, 7524-7532. [CrossRef] [PubMed]
126. Komatsu, M.; Jepson, S.; Arango, M.E.; Carothers Carraway, C.A.; Carraway, K.L. MUC4/sialomucin complex, an intramembrane modulator of ErbB2/HER2/Neu, potentiates primary tumor growth and suppresses apoptosis in a xenotransplanted tumor. Oncogene 2001, 20, 461-470. [CrossRef] [PubMed]
127. Nagy, P.; Friedlander, E.; Tanner, M.; Kapanen, A.I.; Carraway, K.L.; Isola, J.; Jovin, T.M. Decreased Accessibility and Lack of Activation of ErbB2 in JIMT-1, a Herceptin-Resistant, MUC4-Expressing Breast Cancer Cell Line. Cancer Res. 2005, 65, 473-482. [PubMed]
128. Workman, H.C.; Sweeney, C.; Carraway, K.L., 3rd. The Membrane Mucin Muc4 Inhibits Apoptosis Induced by Multiple Insults via ErbB2-Dependent and ErbB2-Independent Mechanisms. Cancer Res. 2009, 69, 2845-2852. [CrossRef] [PubMed]
129. Zhi, X.; Tao, J.; Xie, K.; Zhu, Y.; Li, Z.; Tang, J.;Wang,W.; Xu, H.; Zhang, J.; Xu, Z. MUC4-induced nuclear translocation of β-catenin: A novel mechanism for growth, metastasis and angiogenesis in pancreatic cancer. Cancer Lett. 2014, 346, 104-113. [CrossRef] [PubMed]
130. Tang, J.; Zhu, Y.; Xie, K.; Zhang, X.; Zhi, X.; Wang, W.; Li, Z.; Zhang, Q.; Wang, L.; Wang, J.; et al. The role of the AMOP domain in MUC4/Y-promoted tumour angiogenesis and metastasis in pancreatic cancer. J. Exp. Clin. Cancer Res. 2016, 35, 91. [CrossRef] [PubMed]
131. Chaturvedi, P.; Singh, A.P.; Moniaux, N.; Senapati, S.; Chakraborty, S.; Meza, J.L.; Batra, S.K. MUC4 Mucin Potentiates Pancreatic Tumor Cell Proliferation, Survival, and Invasive Properties and Interferes with Its Interaction to Extracellular Matrix Proteins. Mol. Cancer Res. 2007, 5, 309-320. [CrossRef] [PubMed]
132. Senapati, S.; Gnanapragassam, V.S.; Moniaux, N.; Momi, N.; Batra, S.K. Role of MUC4-NIDO domain in the MUC4-mediated metastasis of pancreatic cancer cells. Oncogene 2012, 31, 3346-3356. [CrossRef] [PubMed]
133. O’Brien, T.J.; Beard, J.B.; Underwood, L.J.; Shigemasa, K. The CA 125 Gene: A Newly Discovered Extension of the Glycosylated N-terminal Domain Doubles the Size of This Extracellular Superstructure. Tumour Biol. 2002, 23, 154-169. [PubMed]
134. Haridas, D.; Ponnusamy, M.P.; Chugh, S.; Lakshmanan, I.; Seshacharyulu, P.; Batra, S.K. MUC16: molecular analysis and its functional implications in benign and malignant conditions. FASEB J. 2014, 28, 4183-4199. [CrossRef] [PubMed]
135. O’Brien, T.J.; Beard, J.B.; Underwood, L.J.; Dennis, R.A.; Santin, A.D.; York, L. The CA 125 Gene:An Extracellular Superstructure Dominated by Repeat Sequences. Tumour Biol. 2001, 22, 348-366. [PubMed]
136. Rao, T.D.; Tian, H.; Ma, X.; Yan, X.; Thapi, S.; Schultz, N.; Rosales, N.; Monette, S.; Wang, A.; Hyman, D.M.; et al. Expression of the Carboxy-Terminal Portion of MUC16/CA125 Induces Transformation and Tumor Invasion. PLoS ONE 2015, 10, e0126633. [CrossRef] [PubMed]
137. Bruney, L.; Conley, K.C.; Moss, N.M.; Liu, Y.; Stack, M.S. Membrane-type I matrix metalloproteinase-dependent ectodomain shedding of mucin16/CA-125 on ovarian cancer cells modulates adhesion and invasion of peritoneal mesothelium. Biol. Chem. 2014, 395, 1221-1231. [CrossRef] [PubMed]
138. Lakshmanan, I.; Ponnusamy, M.P.; Das, S.; Chakraborty, S.; Haridas, D.; Mukhopadhyay, P.; Lele, S.M.; Batra, S.K. MUC16 induced rapid G2/M transition via interactions with JAK2 for increased proliferation and anti-apoptosis in breast cancer cells. Oncogene 2012, 31, 805-817. [CrossRef] [PubMed]
139. Das, S.; Rachagani, S.; Torres-Gonzalez, M.P.; Lakshmanan, I.; Majhi, P.D.; Smith, L.M.; Wagner, K.U.; Batra, S.K. Carboxyl-terminal domain of MUC16 imparts tumorigenic and metastatic functions through nuclear translocation of JAK2 to pancreatic cancer cells. Oncotarget 2015, 6, 5772-5787. [CrossRef] [PubMed]
140. Theriault, C.; Pinard, M.; Comamala, M.; Migneault, M.; Beaudin, J.; Matte, I.; Boivin, M.; Piche, A.; Rancourt, C. MUC16 (CA125) regulates epithelial ovarian cancer cell growth, tumorigenesis and metastasis. Gynecol. Oncol. 2011, 121, 434-443. [CrossRef] [PubMed]
141. Comamala, M.; Pinard, M.; Theriault, C.; Matte, I.; Albert, A.; Boivin, M.; Beaudin, J.; Piche, A.; Rancourt, C. Downregulation of cell surface CA125/MUC16 induces epithelial-to-mesenchymal transition and restores EGFR signalling in NIH:OVCAR3 ovarian carcinoma cells. Br. J. Cancer 2011, 104, 989-999. [CrossRef] [PubMed]
142. Giannakouros, P.; Comamala, M.; Matte, I.; Rancourt, C.; Piche, A. MUC16 mucin (CA125) regulates the formation of multicellular aggregates by altering β-catenin signaling. Am. J. Cancer Res. 2015, 5, 219-230. [PubMed]
143. Burford, B.; Gentry-Maharaj, A.; Graham, R.; Allen, D.; Pedersen, J.W.; Nudelman, A.S.; Blixt, O.; Fourkala, E.O.; Bueti, D.; Dawnay, A.; et al. Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer. Br. J. Cancer 2013, 108, 2045-2055. [CrossRef] [PubMed]
144. Wandall, H.H.; Blixt, O.; Tarp, M.A.; Pedersen, J.W.; Bennett, E.P.; Mandel, U.; Ragupathi, G.; Livingston, P.O.; Hollingsworth, M.A.; Taylor-Papadimitriou, J.; et al. Cancer Biomarkers Defined by Autoantibody Signatures to Aberrant O-Glycopeptide Epitopes. Cancer Res. 2010, 70, 1306-1313. [CrossRef] [PubMed]
145. Pathangey, L.B.; Lakshminarayanan, V.; Suman, V.J.; Pockaj, B.A.; Mukherjee, P.; Gendler, S.J. Aberrant Glycosylation of Anchor-Optimized MUC1 Peptides Can Enhance Antigen Binding Affinity and Reverse Tolerance to Cytotoxic T Lymphocytes. Biomolecules 2016, 6. [CrossRef] [PubMed]
146. Posey, A.D., Jr.; Schwab, R.D.; Boesteanu, A.C.; Steentoft, C.; Mandel, U.; Engels, B.; Stone, J.D.; Madsen, T.D.; Schreiber, K.; Haines, K.M.; et al. Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma. Immunity 2016, 44, 1444-1454. [CrossRef] [PubMed]
147. Rachagani, S.; Torres, M.P.; Moniaux, N.; Batra, S.K. Current status of mucins in the diagnosis and therapy of cancer. Biofactors 2009, 35, 509-527. [CrossRef] [PubMed]
148. Felder, M.; Kapur, A.; Gonzalez-Bosquet, J.; Horibata, S.; Heintz, J.; Albrecht, R.; Fass, L.; Kaur, J.; Hu, K.; Shojaei, H.; et al. MUC16 (CA125): Tumor biomarker to cancer therapy, a work in progress. Mol. Cancer 2014, 13, 129. [CrossRef] [PubMed]
149. Kawa, S.; Kato, M.; Oguchi, H.; Hsue, G.L.; Kobayashi, T.; Koiwai, T.; Tokoo, M.; Furuta, S.; Ichikawa, T.; Kanai, M. Clinical Evaluation of Pancreatic Cancer-Associated Mucin Expressing CA19-9, CA50, SPAN-1, sialyl SSEA-1, and Dupan-2. Scand. J. Gastroenterol. 1992, 27, 635-643. [CrossRef] [PubMed]
150. Cooper, E.H.; Forbes, M.A.; Taylor, M. An evaluation of DUPAN-2 in pancreatic cancer and gastrointestinal disease. Br. J. Cancer 1990, 62, 1004-1005. [CrossRef] [PubMed]
151. Beatson, R.; Maurstad, G.; Picco, G.; Arulappu, A.; Coleman, J.; Wandell, H.H.; Clausen, H.; Mandel, U.; Taylor-Papadimitriou, J.; Sletmoen, M.; et al. The Breast Cancer-Associated Glycoforms of MUC1, MUC1-Tn and sialyl-Tn, Are Expressed in COSMC Wild-Type Cells and Bind the C-Type Lectin MGL. PLoS ONE 2015, 10, e0125994. [CrossRef] [PubMed]
152. Napoletano, C.; Rughetti, A.; Agervig Tarp, M.P.; Coleman, J.; Bennett, E.P.; Picco, G.; Sale, P.; Denda-Nagai, K.; Irimura, T.; Mandel, U.; et al. Tumor-Associated Tn-MUC1 Glycoform Is Internalized through the Macrophage Galactose-Type C-Type Lectin and Delivered to the HLA Class I and II Compartments in Dendritic Cells. Cancer Res. 2007, 67, 8358-8367. [CrossRef] [PubMed]
153. Saeland, E.; van Vliet, S.J.; Backstrom, M.; van den Berg, V.C.; Geijtenbeek, T.B.; Meijer, G.A.; van Kooyk, Y. The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma. Cancer Immunol. Immunother. 2007, 56, 1225-1236. [CrossRef] [PubMed]
154. Van Vliet, S.J.; Gringhuis, S.I.; Geijtenbeek, T.B.; van Kooyk, Y. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45. Nat. Immunol. 2006, 7, 1200-1208. [CrossRef] [PubMed]
155. Gubbels, J.A.; Felder, M.; Horibata, S.; Belisle, J.A.; Kapur, A.; Holden, H.; Petrie, S.; Migneault, M.; Rancourt, C.; Connor, J.P.; et al. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells. Mol. Cancer 2010, 9, 11. [CrossRef] [PubMed]
156. Menon, B.B.; Kaiser-Marko, C.; Spurr-Michaud, S.; Tisdale, A.S.; Gipson, I.K. Suppression of Toll-like receptor-mediated innate immune responses at the ocular surface by the membrane-associated mucins MUC1 and MUC16. Mucosal Immunol. 2015, 8, 1000-1008. [CrossRef] [PubMed]
157. Madsen, C.B.; Lavrsen, K.; Steentoft, C.; Vester-Christensen, M.B.; Clausen, H.; Wandall, H.H.; Pedersen, A.E. Glycan Elongation Beyond the Mucin Associated Tn Antigen Protects Tumor Cells from Immune-Mediated Killing. PLoS ONE 2013, 8, e72413. [CrossRef]
158. Geng, Y.; Yeh, K.; Takatani, T.; King, M.R. Three to Tango: MUC1 as a Ligand for Both E-Selectin and ICAM-1 in the Breast Cancer Metastatic Cascade. Front. Oncol. 2012, 2, 76. [CrossRef] [PubMed]
159. Chen, S.H.; Dallas, M.R.; Balzer, E.M.; Konstantopoulos, K. Mucin 16 is a functional selectin ligand on pancreatic cancer cells. FASEB J. 2012, 26, 1349-1359. [CrossRef] [PubMed]
160. Coupland, L.A.; Parish, C.R. Platelets, Selectins, and the Control of Tumor Metastasis. Semin. Oncol. 2014, 41, 422-434. [CrossRef] [PubMed]