title: MUC1 and MUC4: switching the emphasis from large to small.
abstract: The MUC1 and MUC4 membrane mucins are each composed of a large alpha (α) and a small beta (β) subunit. The α subunits are fully exposed at the cell surface and contain variable numbers of repeated amino acid sequences that are heavily glycosylated. In contrast, the β subunits are much smaller and are anchored within the cell membrane, with their amino-terminal portions exposed at the cell surface and their carboxy-terminal tails facing the cytosol. Studies over the last several years are challenging the long-held belief that α subunits play the predominant role in cancer by conferring cellular properties that allow tumor cells to evade immune recognition and destruction. Indeed, the β subunits of MUC1 and MUC4 have emerged as oncogenes, as they engage signaling pathways responsible for tumor initiation and progression. Thus, a switch in the emphasis from the large α to the small β subunits offers attractive possibilities for successful clinical application. Such a focus shift is further supported by the absence of allelic polymorphism and variable glycosylation in the β subunit as well as by the presence of the β subunit in most MUC1 and MUC4 isoforms expressed by tumors. MUC1α, also known as CA15.3, is a Food and Drug Administration-approved serum biomarker for breast cancer, but its use is no longer recommended by the American Society of Clinical Oncology. However, comparison of β subunit expression in normal and malignant breast tissues may offer a novel approach to the exploitation of membrane mucins as biomarkers, as MUC1β-induced gene signatures with prognostic and predictive values in breast cancer have been reported. Preclinical studies with peptides that interfere with MUC1β oncogenic functions also look promising.
authors: Department of Public Health Sciences, University of California Davis Cancer Center, Sacramento, California 95817, USA. huguette.albrecht@ucdmc.ucdavis.edu
authors: Huguette
authors: H
authors: Albrecht
authors: Kermit L
authors: KL
authors: Carraway
mesh_terms: D000483:Alleles; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D018396:Mucin-1 / Q000096:biosynthesis*; D055264:Mucin-4 / Q000096:biosynthesis*; D011110:Polymorphism, Genetic; D011379:Prognosis; D020033:Protein Isoforms; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; C524658:MUC4 protein, human; D018396:Mucin-1; D055264:Mucin-4; D020033:Protein Isoforms