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.