Epithelial cell adhesion molecule (EpCAM), a transmembrane glycoprotein expressed in stem and epithelial cells, plays a key role in cell proliferation, differentiation and adhesion. It was initially established as a calcium independent, homophilic cell-cell adhesion molecule. Trans-tetramerization through homo-oligomerization of two cis-dimers on opposing cells has been accepted as the underlying mechanism of cell-cell contact formation. This process was, however, never described in detail and structural characterization of trans-tetramers was incomplete. Our comprehensive study of EpCAM oligomerization revealed that EpCAM cis-dimers in fact don't form higher-order oligomers and that EpCAM can thus not function as a homophilic cell-cell adhesion molecule. In the scientific community, EpCAM has been accepted as a homophilic cell adhesion molecule for more than 20 years. Our results, which prove the opposite, present an important breakthrough in the field and explain many previously seemningly ANG contradicting observations regarding the proteins function in cellular processes. This will enable a more proper description of EpCAM's actuall role and in turn lead to a significant progress in our understanding of epithelial morphogenesis and in utilization of EpCAM as a target for carcinoma diagnostics and treatement.
COBISS.SI-ID: 1537878979
Head and neck squamous cell carcinomas (HNSCC) are very heterogeneous and often exhibit severe therapy resistance. Epithelial-mesenchymal-transition (EMT) is a major parameter of poor clinical outcome in those cancers and presents a key hallmark of cancer progression. Epidermal Growth Factor Receptor (EGFR) and Epithelial Cell Adhesion Molecule (EpCAM) are often overexpressed in HNSCC and thus utilized as tumor markers. We showed EGF/EGFR can induce EMT in a concentration-depended manner. Furthermore, we showed that soluble EpCAM's ectodomain acts as a ligand for EGFR and activates pERK1/2 and pATK, while it simultaneously represses EGF-mediated EMT. This newly identified cross-talk between EGFR and EpCAM represent a promising target to improve patient-tailored treatment of head and neck cancers. EMT is an important process in cancer progression, not only in HNSCC, but in numerous other carcinomas as well. Elucidating the mechanism of EMT will provide crucial information on carcinoma development and progression. Identification of a completely novel ANG interaction between two very important carcinoma markers presents an important step along this way and calls for a more detailed biochemical and structural characterization of the protein complex. Status excellence, outstanding scientific achievement, IF 9.163
COBISS.SI-ID: 1537936067