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      Altered Mucins (MUC) Trafficking in Benign and Malignant Conditions

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          Abstract

          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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          Most cited references 104

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          Trastuzumab--mechanism of action and use in clinical practice.

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            Mucins in cancer: function, prognosis and therapy.

             Donald Kufe (2009)
            Epithelia are protected from adverse conditions by a mucous barrier. The secreted and transmembrane mucins that constitute the mucous barrier are largely unrecognized as effectors of carcinogenesis. However, both types of mucins are intimately involved in inflammation and cancer. Moreover, diverse human malignancies overexpress transmembrane mucins to exploit their role in signalling cell growth and survival. Mucins have thus been identified as markers of adverse prognosis and as attractive therapeutic targets. Notably, the findings that certain transmembrane mucins induce transformation and promote tumour progression have provided the experimental basis for demonstrating that inhibitors of their function are effective as anti-tumour agents in preclinical models.
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              Lysosomes: fusion and function.

              Lysosomes are dynamic organelles that receive and degrade macromolecules from the secretory, endocytic, autophagic and phagocytic membrane-trafficking pathways. Live-cell imaging has shown that fusion with lysosomes occurs by both transient and full fusion events, and yeast genetics and mammalian cell-free systems have identified much of the protein machinery that coordinates these fusion events. Many pathogens that hijack the endocytic pathways to enter cells have evolved mechanisms to avoid being degraded by the lysosome. However, the function of lysosomes is not restricted to protein degradation: they also fuse with the plasma membrane during cell injury, as well as having more specialized secretory functions in some cell types.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                September 2014
                26 August 2014
                : 5
                : 17
                : 7272-7284
                Affiliations
                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.
                Author notes
                Correspondence to: Dr. Surinder K. Batra, sbatra@ 123456unmc.edu
                4202122
                25261375
                Copyright: © 2014 Joshi et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Categories
                Review

                Oncology & Radiotherapy

                endocytosis, plasma membrane, trafficking, mucins, cancer

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