The Molecular Mechanisms of EpCAM Activation and Signaling in Tumorigenesis
Date Issued
2015
Date
2015
Author(s)
Tso, Hsien-Cheng
Abstract
Epithelial cell adhesion molecule (EpCAM) is a type Ⅰ transmembrane glycoprotein overexpressed in almost all adenocarcinomas and squamous cell carcinomas. It’s also a well-known cancer stem cell marker and contributes to tumor growth. EpCAM is highly expressed in colon cancer. Our previous study pointed out that EpCAM plays an important role in regulating tumorigenesis in colon cancer stem cells and in regulating tumor malignancy. In this study, we identified the signaling of EpCAM through receptor tyrosine kinase array and found that EpCAM extracellular domain (EpEX) might activate c-Met signaling, which promotes cell proliferation, migration, invasion and colony formation. Subsequent study of EpEX signaling pathway found that EpEX activated the c-Met-ERK signaling pathway and increased the activity of TACE and γ-secretase. Moreover, to investigate the genes regulated by EpICD using ChIP Assay, we successfully generated three monoclonal antibodies against EpICD by hybridoma technology. EpEX was found to upregulate EpICD and c-Myc by increasing γ-secretase activity. EpICD could regulate the nuclear translocation of β-catenin-FHL2 complex then decrease the down-stream gene expression. In conclusion, our results indicate that EpCAM can regulate tumorigenesis through production of EpEX and EpICD. EpEX can activate the c-Met-ERK signaling pathway, while EpICD can turn on gene expression after being translocated into the nucleus.
Subjects
colorectal cancer
EpCAM
EpEX
EpICD
c-Met
SDGs
Type
thesis