Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, R8:04 Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
Biochem Biophys Res Commun. 2013 Sep 20;439(2):203-8. doi: 10.1016/j.bbrc.2013.08.059. Epub 2013 Aug 26.
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.
上皮细胞黏附分子 (EpCAM) 是一种上皮细胞和癌细胞的“标志物”，其信号作用的累积和不断增长的证据。其重要性已被确认为乳腺癌干细胞表型的一部分，致瘤性乳腺癌干细胞是 EpCAM(+)。尽管它在正常细胞发育和癌症中具有复杂的功能，但对 EpCAM 相互作用蛋白的了解相对较少。我们使用乳腺癌细胞系进行 EpCAM 共免疫沉淀，然后进行质谱分析，以寻找新的潜在相互作用蛋白。内质网氨肽酶 2 (ERAP2) 被发现与 EpCAM 共沉淀，并在细胞质/内质网和质膜中共定位。ERAP2 是一种位于内质网 (ER) 中的蛋白水解酶，在 MHC Ⅰ类分子呈递肽段的修剪中起着核心作用。在存在狗胰腺粗微粒体 (ER 囊泡) 的情况下，体外表达 EpCAM 和 ERAP2 证实了 N 连接糖基化、内质网中的加工和 EpCAM 的大小。ERAP2 与 EpCAM 的关联是一个独特而新颖的发现，为 EpCAM 加工以及癌症中抗原呈递如何被调控提供了新的思路。
