Dual Role of the Extracellular Domain of Human Mucin MUC1 in Metastasis

ABSTRACT Human mucin MUC1 plays an important role in cancer development. The increased level of this molecule expression during cancer cell progression induces metastasis and is associated with poor prognosis for patients. There is a large body of experimental data on the role of various functional domains of human mucin MUC1 in metastasis. While, the cytoplasmic domain determined to play a definitive role, the influence of extracellular domain on cancer cell invasiveness still remains unclear. The present paper reveals that the extracellular domain of MUC1 molecule consists of two functional subdomains—the region of tandem repeats (TR) and the region of irregular repeats (IR). We demonstrate the ability of each of these subdomains to alter the invasiveness of cancer cells. The presence of the MUC1 molecules containing TR subdomain (MUC1‐TR) on the surface of low‐invasive cancer cells leads to the increase in their transendothelial migration potency, while the addition of the IR subdomain to the MUC1‐TR molecule (MUC1‐IR‐TR) restores their natural low invasiveness. J. Cell. Biochem. 118: 4002–4011, 2017. © 2017 Wiley Periodicals, Inc. Schematic representation of molecular mechanisms of interaction between the endothelial cells and HT‐29 cells bearing different subdomains of the mucin MUC1 ectodomain. The presence of the MUC1 molecules containing TR subdomain (MUC1‐TR) on the surface of low‐invasive cancer cells leads to the increase in their transendothelial migration potency, while the addition of the IR subdomain to the MUC1‐TR molecule (MUC1‐IR‐TR) restores their natural low invasiveness.