Mucin 13: structure, function, and potential roles in cancer pathogenesis

Abstract

Mucin 13 (MUC13) is a high-molecular-weight transmembrane glycoprotein that is frequently and aberrantly expressed in a variety of epithelial carcinomas, including gastric, colorectal, and ovarian cancers. On the basis of the high expression of MUC13 in cancer cells as well as recent laboratory findings suggesting a malignant phenotype of MUC13-transfected cell lines, the oncogenic potential of MUC13 has emerged. The various functional domains of MUC13 may confer oncogenic potential to MUC13. For example, the bulky extracellular domain with extensive modification with glycan chains may prevent cell-cell and cell-extracellular matrix binding whereas the cytoplasmic tail containing serine and tyrosine residues for potential phosphorylation may participate in cell signaling. MUC13 exhibits the characteristics suitable as an early marker for cancer screening and presents a promising target for antibody-guided targeted therapy.

Figure 1

Schematic diagram and annotated amino acid sequence of MUC13. Left, a schematic diagram showing the structural features of MUC13 protein. The signal peptide, mucin repeat domain, SEA module, EGF-like domains, TM domain, and the cytoplasmic domain are shown from N-terminal (top) to C-terminal (bottom). Right, the amino acid sequence of MUC13 indicating amino acid residues for predicted posttranslational modification (O-glycosylation, N-glycosylation, and disulfide bonds). The signal peptide, SEA module, and TM sequences are indicated by text that is underlined, bold and underlined, and in italics font, respectively.

Figure 2

Normal and atypical cellular expression of MUC13. Left, as a TM mucin, theoretically MUC13 is processed through the endoplasmic reticulum (ER) and Golgi apparatus, where posttranslational modifications such as the addition of O- and N-glycosylation occurs and the protein is delivered to the apical cell surface. Right, in cancer cells, MUC13 is localized at basal, lateral, and apical cell surface membranes, which possibly contributes to the loss of cell–cell and cell–ECM binding. Hypothetically, aberrant subcellular localization of MUC13 may alter cell signaling due to interaction with EGFRs. These events could increase tumorigenesis, cell invasion, and metastasis.