Abstract
Regulated intramembrane proteolysis of epithelial cell adhesion molecule (EpCAM) results in shedding of the extracellular domain (EpEX) and release of the intra-cellular domain (EpICD) into the cytoplasm. Released EpICD associates with FHL2, β-catenin and Lef-1 to form a nuclear complex and triggers oncogenic signaling. This study was conducted to examine the nuclear expression of EpICD in hepatocellular carcinoma (HCC) and to assess the role of EpICD in HCC. EpICD immunoexpression was examined in 100cases of HCC using tissue microarrays and correlated with clinicopathological parameters. We also examined the role of EpICD in HCC using EpICD cDNA transfected HCC cell line and EpCAM silenced HCC cell line by small interfering RNA (siRNA). Nuclear expression of EpICD was observed in 19 of 100 (19%) cases. Nuclear expression of EpICD significantly correlated with nuclear expression of β-catenin, and Ki-67 labeling index. In addition, nuclear expression of EpICD was associated with higher histologic grade and advanced Tcategory. Forced overexpression of EpICD in the HCC cell significantly increased the cell proliferation, migration and invasion. The overexpression of EpICD also increased the expression levels of the active form of β-catenin and c-myc and cyclinD1. In contrast, downregulation of EpCAM by siRNA decreased the cell proliferation, migration, invasion and the expression of active form of β-catenin, c-myc and cyclinD1. Our present data suggest that EpICD plays important roles in HCC progression by modulating expression of target genes of EpCAM.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death worldwide [1]
EpEx expression was detected in park et al: NUCLEAR EpICD EXPRESSION IN HEPATOCELLULAR CARCINOMA
We determined the role of EpICD and the clinical significance of nuclear expression of EpICD in HCC
Summary
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death worldwide [1]. Considering the current limited therapy options for HCC, finding a new therapeutic target molecule has become very important. Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that functions as a hemophilic, epithelial-specific intercellular cell-adhesion molecule [3]. EpCAM is expressed in several human epithelial tissues and cancers, including HCC and progenitor and stem cells [4,5]. The presence of a high amount of membranous EpCAM in various cancers has rendered EpCAM an ideal target for immunotherapy [4,6]. Despite the broad distribution of EpCAM in human malignancies, results from recent clinical trials of EpCAM-specific monoclonal antibodies have shown limited efficacy [7,8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
