title: A minimal fragment of MUC1 mediates growth of cancer cells.
abstract: The MUC1 protein is aberrantly expressed on many solid tumor cancers. In contrast to its apical clustering on healthy epithelial cells, it is uniformly distributed over cancer cells. However, a mechanistic link between aberrant expression and cancer has remained elusive. Herein, we report that a membrane-bound MUC1 cleavage product, that we call MUC1*, is the predominant form of the protein on cultured cancer cells and on cancerous tissues. Further, we demonstrate that transfection of a minimal fragment of MUC1, MUC1*(1110), containing a mere forty-five (45) amino acids of the extracellular domain, is sufficient to confer the oncogenic activities that were previously attributed to the full-length protein. By comparison of molecular weight and function, it appears that MUC1* and MUC1*(1110) are approximately equivalent. Evidence is presented that strongly supports a mechanism whereby dimerization of the extracellular domain of MUC1* activates the MAP kinase signaling cascade and stimulates cell growth. These findings suggest methods to manipulate this growth mechanism for therapeutic interventions in cancer treatments.
authors.affiliation: Minerva Biotechnologies, Waltham, Massachusetts, United States of America.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Mahanta
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Fessler
authors.forename: Jaehong
authors.initials: J
authors.lastname: Park
authors.forename: Cynthia
authors.initials: C
authors.lastname: Bamdad
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D017978:Receptors, Growth Factor / Q000378:metabolism
chemical_list: D000906:Antibodies; D008024:Ligands; D018396:Mucin-1; D050505:Mutant Proteins; D010446:Peptide Fragments; D017978:Receptors, Growth Factor