Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Mucins (MUCs)

  • Rahat Jahan
  • Sukhwinder Kaur
  • Muzafar A. Macha
  • Surinder K. Batra
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101739
This is a preview of subscription content, log in to check access.

References

  1. Apostolopoulos V, Stojanovska L, Gargosky SE. MUC1 (CD227): a multi-tasked molecule. Cell Mol Life Sci. 2015;72:4475–500. doi:10.1007/s00018-015-2014-z.CrossRefGoogle Scholar
  2. Bast Jr RC, Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981;68:1331–7.PubMedPubMedCentralGoogle Scholar
  3. Chaturvedi P, Singh AP, Batra SK. Structure, evolution, and biology of the MUC4 mucin. FASEB J. 2008;22:966–81. doi:10.1096/fj.07-9673rev.CrossRefGoogle Scholar
  4. Das S, Batra SK. Understanding the unique attributes of MUC16 (CA125): potential implications in targeted therapy. Cancer Res. 2015;75:4669–74. doi:10.1158/0008-5472.CAN-15-1050.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Das S, Rachagani S, Sheinin Y, Smith LM, Gurumurthy CB, Roy HK, Batra SK. Mice deficient in Muc4 are resistant to experimental colitis and colitis-associated colorectal cancer. Oncogene. 2016;35:2645–54. doi:10.1038/onc.2015.327.CrossRefGoogle Scholar
  6. Felder M, Kapur A, Gonzalez-Bosquet J, Horibata S, Heintz J, Albrecht R, Fass L, Kaur J, Hu K, Shojaei H, Whelan RJ, Patankar MS. MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress. Mol Cancer. 2014;13:129. doi:10.1186/1476-4598-13-129.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Gum Jr JR, Crawley SC, Hicks JW, Szymkowski DE, Kim YS. MUC17, a novel membrane-tethered mucin. Biochem Biophys Res Commun. 2002;291:466–75. doi:10.1006/bbrc.2002.6475.CrossRefGoogle Scholar
  8. Hanson RL, Hollingsworth MA. Functional consequences of differential O-glycosylation of MUC1, MUC4, and MUC16 (downstream effects on signaling). Biomolecules. 2016; 6. doi:10.3390/biom6030034.CrossRefPubMedCentralGoogle Scholar
  9. Haridas D, Ponnusamy MP, Chugh S, Lakshmanan I, Seshacharyulu P, Batra SK. MUC16: molecular analysis and its functional implications in benign and malignant conditions. FASEB J. 2014;28:4183–99. doi:10.1096/fj.14-257352.CrossRefGoogle Scholar
  10. Hasegawa M, Sinha RK, Kumar M, Alam M, Yin L, Raina D, Kharbanda A, Panchamoorthy G, Gupta D, Singh H, Kharbanda S, Kufe D. Intracellular targeting of the oncogenic MUC1-C protein with a novel GO-203 nanoparticle formulation. Clin Cancer Res. 2015;21:2338–47. doi:10.1158/1078-0432.CCR-14-3000.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Hisatsune A, Nakayama H, Kawasaki M, Horie I, Miyata T, Isohama Y, Kim KC, Katsuki H. Anti-MUC1 antibody inhibits EGF receptor signaling in cancer cells. Biochem Biophys Res Commun. 2011;405:377–81. doi:10.1016/j.bbrc.2011.01.029.CrossRefGoogle Scholar
  12. Ho SB, Dvorak LA, Moor RE, Jacobson AC, Frey MR, Corredor J, Polk DB, Shekels LL. Cysteine-rich domains of muc3 intestinal mucin promote cell migration, inhibit apoptosis, and accelerate wound healing. Gastroenterology. 2006;131:1501–17.Google Scholar
  13. Huang L, Chen D, Liu D, Yin L, Kharbanda S, Kufe D. MUC1 oncoprotein blocks glycogen synthase kinase 3beta-mediated phosphorylation and degradation of beta-catenin. Cancer Res. 2005;65:10413–22. doi:10.1158/0008-5472.CAN-05-2474.CrossRefGoogle Scholar
  14. Joshi S, Kumar S, Bafna S, Rachagani S, Wagner KU, Jain M, Batra SK. Genetically engineered mucin mouse models for inflammation and cancer. Cancer Metastasis Rev. 2015;34:593–609. doi:10.1007/s10555-015-9549-1.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Kitamoto S, Yokoyama S, Higashi M, Yamada N, Matsubara S, Takao S, Batra SK, Yonezawa S. Expression of MUC17 is regulated by HIF1alpha-mediated hypoxic responses and requires a methylation-free hypoxia responsible element in pancreatic cancer. PLoS One. 2012;7:e44108. doi:10.1371/journal.pone.0044108.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer. 2009;9:874–85. doi:10.1038/nrc2761.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Luu Y, Junker W, Rachagani S, Das S, Batra SK, Heinrikson RL, Shekels LL, Ho SB. Human intestinal MUC17 mucin augments intestinal cell restitution and enhances healing of experimental colitis. Int J Biochem Cell Biol. 2010;42:996–1006. doi:10.1016/j.biocel.2010.03.001.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Malmberg EK, Pelaseyed T, Petersson AC, Seidler UE, De JH, Riordan JR, Hansson GC. The C-terminus of the transmembrane mucin MUC17 binds to the scaffold protein PDZK1 that stably localizes it to the enterocyte apical membrane in the small intestine. Biochem J. 2008;410:283–9. doi:10.1042/BJ20071068.CrossRefGoogle Scholar
  19. Moniaux N, Junker WM, Singh AP, Jones AM, Batra SK. Characterization of human mucin MUC17. Complete coding sequence and organization. J Biol Chem. 2006;281:23676–85. doi:10.1074/jbc.M600302200.CrossRefGoogle Scholar
  20. Moniaux N, Nollet S, Porchet N, Degand P, Laine A, Aubert JP. Complete sequence of the human mucin MUC4: a putative cell membrane-associated mucin. Biochem J. 1999;338(Pt 2):325–33.PubMedPubMedCentralGoogle Scholar
  21. Muniyan S, Haridas D, Chugh S, Rachagani S, Lakshmanan I, Gupta S, Seshacharyulu P, Smith LM, Ponnusamy MP, Batra SK. MUC16 contributes to the metastasis of pancreatic ductal adenocarcinoma through focal adhesion mediated signaling mechanism. Genes Cancer. 2016;7:110–24. doi:10.18632/genesandcancer.104.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Obermair A, Schmid BC, Packer LM, Leodolter S, Birner P, Ward BG, Crandon AJ, McGuckin MA, Zeillinger R. Expression of MUC1 splice variants in benign and malignant ovarian tumours. Int J Cancer. 2002;100:166–71. doi:10.1002/ijc.10456.CrossRefGoogle Scholar
  23. Pillai K, Pourgholami MH, Chua TC, Morris DL. MUC1 as a potential target in anticancer therapies. Am J Clin Oncol. 2015;38:108–18. doi:10.1097/COC.0b013e31828f5a07.CrossRefGoogle Scholar
  24. Rahn JJ, Shen Q, Mah BK, Hugh JC. MUC1 initiates a calcium signal after ligation by intercellular adhesion molecule-1. J Biol Chem. 2004;279:29386–90. doi:10.1074/jbc.C400010200.CrossRefGoogle Scholar
  25. Ramasamy S, Duraisamy S, Barbashov S, Kawano T, Kharbanda S, Kufe D. The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop. Mol Cell. 2007;27:992–1004. doi:10.1016/j.molcel.2007.07.031.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Rubinstein DB, Karmely M, Pichinuk E, Ziv R, Benhar I, Feng N, Smorodinsky NI, Wreschner DH. The MUC1 oncoprotein as a functional target: immunotoxin binding to alpha/beta junction mediates cell killing. Int J Cancer. 2009;124:46–54. doi:10.1002/ijc.23910.CrossRefGoogle Scholar
  27. Senapati S, Gnanapragassam VS, Moniaux N, Momi N, Batra SK. Role of MUC4-NIDO domain in the MUC4-mediated metastasis of pancreatic cancer cells. Oncogene. 2012;31:3346–56. doi:10.1038/onc.2011.505.CrossRefGoogle Scholar
  28. Shen Q, Rahn JJ, Zhang J, Gunasekera N, Sun X, Shaw AR, Hendzel MJ, Hoffman P, Bernier A, Hugh JC. MUC1 initiates Src-CrkL-Rac1/Cdc42-mediated actin cytoskeletal protrusive motility after ligating intercellular adhesion molecule-1. Mol Cancer Res. 2008;6:555–67. doi:10.1158/1541-7786.MCR-07-2033.CrossRefGoogle Scholar
  29. Singh AP, Chaturvedi P, Batra SK. Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy. Cancer Res. 2007;67:433–6. doi:10.1158/0008-5472.CAN-06-3114.CrossRefGoogle Scholar
  30. Tang J, Zhu Y, Xie K, Zhang X, Zhi X, Wang W, Li Z, Zhang Q, Wang L, Wang J, Xu Z. 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. doi:10.1186/s13046-016-0369-0.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Tanida S, Mori Y, Ishida A, Akita K, Nakada H. Galectin-3 binds to MUC1-N-terminal domain and triggers recruitment of beta-catenin in MUC1-expressing mouse 3T3 cells. Biochim Biophys Acta. 2014;1840:1790–7. doi:10.1016/j.bbagen.2014.02.008.CrossRefGoogle Scholar
  32. Wang L, Chen H, Liu F, Madigan MC, Power CA, Hao J, Patterson KI, Pourgholami MH, O’Brien PM, Perkins AC, Li Y. Monoclonal antibody targeting MUC1 and increasing sensitivity to docetaxel as a novel strategy in treating human epithelial ovarian cancer. Cancer Lett. 2011;300:122–33. doi:10.1016/j.canlet.2010.09.013.CrossRefGoogle Scholar
  33. Wang L, Zhi X, Zhu Y, Zhang Q, Wang W, Li Z, Tang J, Wang J, Wei S, Li B, Zhou J, Jiang J, Yang L, Xu H, Xu Z. MUC4-promoted neural invasion is mediated by the axon guidance factor Netrin-1 in PDAC. Oncotarget. 2015;6:33805–22. doi:10.18632/oncotarget.5668.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Wei X, Xu H, Kufe D. MUC1 oncoprotein stabilizes and activates estrogen receptor alpha. Mol Cell. 2006;21:295–305. doi:10.1016/j.molcel.2005.11.030.CrossRefGoogle Scholar
  35. Zhang L, Vlad A, Milcarek C, Finn OJ. Human mucin MUC1 RNA undergoes different types of alternative splicing resulting in multiple isoforms. Cancer Immunol Immunother. 2013;62:423–35. doi:10.1007/s00262-012-1325-2.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Rahat Jahan
    • 1
  • Sukhwinder Kaur
    • 1
  • Muzafar A. Macha
    • 1
    • 2
  • Surinder K. Batra
    • 1
    • 3
    • 4
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of Otolaryngology-Head and Neck SurgeryUniversity of Nebraska Medical CenterOmahaUSA
  3. 3.Buffett Cancer CenterUniversity of Nebraska Medical CenterOmahaUSA
  4. 4.Eppley Institute for Research in Cancer and Allied DiseasesUniversity of Nebraska Medical CenterOmahaUSA