title: Anti-MUC1 antibody inhibits EGF receptor signaling in cancer cells.
abstract: MUC1 is a type I transmembrane glycoprotein aberrantly overexpressed in various cancer cells. High expression of MUC1 is closely associated with cancer progression and metastasis, leading to poor prognosis. We previously reported that MUC1 is internalized by the binding of the anti-MUC1 antibody, from the cell surface to the intracellular region via the macropinocytotic pathway. Since MUC1 is closely associated with ErbBs, such as EGF receptor (EGFR) in cancer cells, we examined the effect of the anti-MUC1 antibody on EGFR trafficking. Our results show that: (1) anti-MUC1 antibody GP1.4, but not another anti-MUC1 antibody C595, triggered the internalization of EGFR in pancreatic cancer cells; (2) internalization of EGFR by GP1.4 resulted in the inhibition of ERK phosphorylation by EGF stimulation, in a MUC1 dependent manner; (3) inhibition of ERK phosphorylation by GP1.4 resulted in the suppression of proliferation and migration of pancreatic cancer cells. We conclude that the internalization of EGFR by anti-MUC1 antibody GP1.4 inhibits the progression of cancer cells via the inhibition of EGFR signaling.
authors.affiliation: Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Kumamoto 862-0973, Japan. hisatsun@kumamoto-u.ac.jp
authors.forename: Akinori
authors.initials: A
authors.lastname: Hisatsune
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Horie
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Isohama
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Kim
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katsuki
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D018396:Mucin-1 / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; C434325:MUC-1 monoclonal antibody; C060192:MUC1 protein, human; D018396:Mucin-1; D066246:ErbB Receptors