MUC1 and MUC4: switching the emphasis from large to small

Cancer Biother Radiopharm. 2011 Jun;26(3):261-71. doi: 10.1089/cbr.2011.1017.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Biomarkers, Tumor
  • Breast Neoplasms / metabolism
  • Carcinoma / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glycosylation
  • Humans
  • Mucin-1 / biosynthesis*
  • Mucin-4 / biosynthesis*
  • Polymorphism, Genetic
  • Prognosis
  • Protein Isoforms
  • Signal Transduction


  • Biomarkers, Tumor
  • MUC4 protein, human
  • Mucin-1
  • Mucin-4
  • Protein Isoforms