Altered Mucins (MUC) Trafficking in Benign and Malignant Conditions
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1 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, U.S.A;
2 Momenta Pharmaceuticals, Inc. Cambridge, MA 02142, USA;
3 Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, U.S.A.
Dr. Surinder K. Batra, e-mail: firstname.lastname@example.org
Keywords: Mucins; cancer; trafficking; endocytosis; plasma membrane
Received: July 18, 2014 Accepted: August 14, 2014 Published: August 26, 2014
Abbreviations: TGN, Trans-Golgi network; ECD, Extracellular domain; TM, Transmembrane; CT, Cytoplasmic tail; NLS, Nuclear localization signal; HSP, Heat shock protein; HRG, Heregulin; Nup62, Nucleoporin 62; EGFR, Epidermal growth factor receptor; FGF1, Fibroblast growth factor; Y, Tyrosine residue; AP-2, Adaptor protein-2.
Mucins are high molecular weight O-glycoproteins that are predominantly expressed at the apical surface of epithelial cells and have wide range of functions. The functional diversity is attributed to their structure that comprises of a peptide chain with unique domains and multiple carbohydrate moieties added during posttranslational modifications. Tumor cells aberrantly overexpress mucins, and thereby promote proliferation, differentiation, motility, invasion and metastasis. Along with their aberrant expression, accumulating evidence suggest the critical role of altered subcellular localization of mucins under pathological conditions due to altered endocytic processes. The mislocalization of mucins and their interactions result in change in the density and activity of important cell membrane proteins (like, receptor tyrosine kinases) to facilitate various signaling, which help cancer cells to proliferate, survive and progress to more aggressive phenotype. In this review article, we summarize studies on mucins trafficking and provide a perspective on its importance to pathological conditions and to answer critical questions including its use for therapeutic interventions.
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