title: MUC1-mediated motility in breast cancer: a review highlighting the role of the MUC1/ICAM-1/Src signaling triad.
abstract: Breast cancer is the most common cancer in women with the leading cause of death being metastasis, the spread of cancer to distant organs. For those patients with high-risk estrogen receptor positive (ER+) breast cancer, an increased expression of the glycoprotein MUC1 is associated with resistance to anti-hormonal therapy, metastasis and death. Tumor cells may use MUC1 to metastasize by exploiting the vascular adhesion pathways used by leukocytes during the inflammatory response. MUC1 is a type 1 transmembrane protein whose cytoplasmic tail acts as a scaffold for several signaling pathways including the non-receptor kinase Src, a signaling molecule involved in cell differentiation, proliferation, adhesion and motility. This review will highlight our current knowledge of how MUC1/ICAM-1 binding can lead to the recruitment and activation of Src and propose a novel role for lipid raft microdomains in this promigratory signaling. Improved understanding of the mechanism of metastases and the underlying signaling cascade is a prerequisite to the discovery of therapeutic targets to prevent metastasis and death in ER+ breast cancer patients.
authors.affiliation: Department of Laboratory of Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Lacey
authors.initials: L
authors.lastname: Haddon
authors.forename: Judith
authors.initials: J
authors.lastname: Hugh
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000473:pathology*; D002465:Cell Movement; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000473:pathology; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D011960:Receptors, Estrogen; D018799:Intercellular Adhesion Molecule-1; D019061:src-Family Kinases