title: A novel therapeutic drug for colon cancer: EpCAM scFv-truncated protamine (tp)-siRNA.
abstract: Colon cancer is a type of malignant tumor that causes considerable mortality worldwide. Epithelial cellular adhesion molecule (EpCAM), a tumor-associated antigen of colon tumors, is a target for colon cancer therapy. EpCAM-specific monoclonal antibodies (mAbs) have been applied in human colon cancer since the 1990s; however, the therapeutic effects are limited. EpCAM activates nuclear signaling pathways by releasing its intracellular domain (EpICD). The released EpICD stimulates the Wnt/β-catenin signaling pathway, which is also strongly associated with tumorigenesis. EpCAM is also a target gene of the Wnt/β-catenin signaling pathway. EpCAM and the Wnt/β-catenin signaling pathway form a functional interaction cycle in colon cancer. Thus, we propose a new therapeutic drug for colon cancer: an EpCAM single-chain fragment variable antibody (scFv)-truncated protamine-siRNA. EpCAM scFv can recognize and bind colon cancer cells through its EpCAM antigen activity. Furthermore, the specific siRNA transferred into colon cancer cells specifically inhibits Wnt/β-catenin signal transmission. Therefore, this new drug may efficiently interrupt the functional cycle between EpCAM and Wnt/β-catenin signaling and be an effective therapeutic strategy for colon cancer.
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, 710069, China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Hao
authors.forename: Yansen
authors.initials: Y
authors.lastname: Zhen
authors.forename: Zaicun
authors.initials: Z
authors.lastname: Wang
authors.forename: Fulin
authors.initials: F
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism / Q000628:therapy*; D000071858:Epithelial Cell Adhesion Molecule; D055785:Gene Knockdown Techniques / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry; D011479:Protamines / Q000737:chemistry*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics*; D057127:Single-Chain Antibodies / Q000737:chemistry*; D014162:Transfection / Q000379:methods; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D010446:Peptide Fragments; D011479:Protamines; D034741:RNA, Small Interfering; D057127:Single-Chain Antibodies
keywords: EpCAM; Wnt/β-catenin; cancer therapy; colon cancer; siRNA; tumor antigen