title: EpCAM associates with endoplasmic reticulum aminopeptidase 2 (ERAP2) in breast cancer cells.
abstract: Epithelial cell adhesion molecule (EpCAM) is an epithelial and cancer cell "marker" and there is a cumulative and growing evidence of its signaling role. Its importance has been recognized as part of the breast cancer stem cell phenotype, the tumorigenic breast cancer stem cell is EpCAM(+). In spite of its complex functions in normal cell development and cancer, relatively little is known about EpCAM-interacting proteins. We used breast cancer cell lines and performed EpCAM co-immunoprecipitation followed by mass spectrometry in search for novel potentially interacting proteins. The endoplasmic reticulum aminopeptidase 2 (ERAP2) was found to co-precipitate with EpCAM and to co-localize in the cytoplasm/ER and the plasma membrane. ERAP2 is a proteolytic enzyme set in the endoplasmic reticulum (ER) where it plays a central role in the trimming of peptides for presentation by MHC class I molecules. Expression of EpCAM and ERAP2 in vitro in the presence of dog pancreas rough microsomes (ER vesicles) confirmed N-linked glycosylation, processing in ER and the size of EpCAM. The association between ERAP2 and EpCAM is a unique and novel finding that provides new ideas on EpCAM processing and on how antigen presentation may be regulated in cancer.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, R8:04 Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Electronic address: Salah.Eldin.Gadalla@ki.se.
authors.forename: Salah-Eldin
authors.initials: SE
authors.lastname: Gadalla
authors.forename: Karin
authors.initials: K
authors.lastname: Öjemalm
authors.forename: Patricia Lara
authors.initials: PL
authors.lastname: Vasquez
authors.forename: Ingmarie
authors.initials: I
authors.lastname: Nilsson
authors.forename: Christer
authors.initials: C
authors.lastname: Ericsson
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Monica
authors.initials: M
authors.lastname: Nistér
mesh_terms: D000626:Aminopeptidases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis / Q000378:metabolism*; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism*; D045744:Cell Line, Tumor; D004285:Dogs; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006031:Glycosylation; D006801:Humans
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D000626:Aminopeptidases; C503944:ERAP2 protein, human
keywords: Cleavage; Co-localization; ERAP2; EpCAM; Glycosylation