Journal of Clinical & Experimental Pathology
Open Access

Abstract

The cellular prion protein (PrP) is a GPI-anchored membrane protein mainly known for its role in fatal neurodegenerative diseases. The mutated form of PrP is the infectious agent of prion disease. The normal PrP protein can be found on many types of normal cells. Our recent data showed that PrP are over-expressed in a subset of human pancreatic ductal adenocarcinoma (PDAC), and the up-regulated PrP exist as a Pro-PrP instead of a mature GPI-anchored PrP. The Pro-PrP has a motif binding filament A, and subsequently disrupts the normal cell skeleton and involves carcinogenesis by facilitating cellular adhesion, migration and invasion. Most importantly, the up-regulation of PrP is a marker of poorer prognosis in PDAC. Recently we found that high PrP expressions in various PDAC cell lines regulate Notch signaling pathway, by up-regulation of the activated Notch1 intracellular domain (NICD), which could form a complex with PrP. The silencing of either component led to the down-regulation of the other partner. Knockdown of PrP in PDAC cell lines induced cancer cell apoptosis, decreased cell invasion and Akt activation, while over-expression of PrP in PDAC cells led to increased NICD and Akt phosphorylation, promoted cell proliferation and invasion. These findings suggest that PrP in certain pancreatic cancer cells promotes tumor survival and invasion through regulating Notch signaling and Akt activation pathway. Future studies will aim to elucidate the mechanisms underlying the cross-talk between PrP and Notch in pancreatic cancer progression, and to explore the therapeutic target of PrP and Notch complex.

Biography

Wei Xin is an attending Physician and Associate Residency Program Director of Pathology at University Hospital Case Medical Center, and Assistant Professor at Case Western Reserve University. He received his medical degree from Shanghai Medical University and Ph.D. from SUNY at Buffalo, and pathology residency training at University of Michigan. During his career, Dr. Xin has published dozens of paper and gave multiple presentation and workshop at national and international meetings. He is also in charge of mice histology at Case Comprehensive Cancer Center and the Director of autopsy service of the university hospital.