title: Role of Notch signaling in colon homeostasis and carcinogenesis.
abstract: Colorectal cancer is a leading cause of cancer-related deaths world-wide. Despite the development of new anticancer agents, there will be an estimated 150,000 new cases and 50,000 deaths associated with this disease during the next year.((1)) This is due, in part, to the limitations of chemotherapy, resulting from drug resistance and organ system toxicities. To overcome the inherent limitations associated with standard chemotherapy techniques, the development of novel drug targets is of utmost importance in combating this disease. There is accumulating evidence that a small fraction of cancer cells, referred to as cancer stem cells, may play a critical role in the pathogenesis of this disease. In fact, the identification of cancer stem cells can be accomplished based on the expression of surface markers associated with a cancer stem-like phenotype. This stem-like phenotype includes indefinite self-replication, pluripotency, and most importantly, resistance to chemotherapeutics. Therefore, understanding the properties of cancer stem cells may ultimately lead to new therapeutic approaches. Recently, several studies have shown that Notch signaling is critical in maintaining cancer stem cell properties. This review provides a summary of colonic crypt organization and colon carcinogenesis with a focus on stem cells. Moreover, we discuss novel therapeutic strategies that are under development for targeting Notch signaling in cancer stem cells.
authors.affiliation: Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000209:etiology*; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000166:cytology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000166:cytology; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
chemical_list: D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D051880:Receptors, Notch; D051153:Wnt Proteins