title: Epigenetic silencing of Notch signaling in gastrointestinal cancers.
abstract: The Notch signaling pathway drives proliferation, differentiation, apoptosis, cell fate choices and maintenance of stem cells during embryogenesis and in self-renewing tissues of the adult. In addition, aberrant Notch signaling has been implicated in several tumors, where Notch can function both as an oncogene or a tumor-suppressor gene, depending on the context.       This Extra View aims to review what is currently known about Notch signaling, in particular in gastrointestinal tumors, providing a summary of our data on Notch1 signaling in gastric cancer with results obtained in colorectal cancer (CRC).   We have already reported that the epigenetic regulation of the Notch ligand DLL1 controls Notch1 signaling activation in gastric cancer, and that Notch1 inhibition is associated with the diffuse type of gastric cancer. Here, we describe additional data showing that in CRC cell lines, unlike gastric cancer, DLL1 expression is not regulated by promoter methylation. Moreover, in CRC, Notch1 receptor is not affected by any mutation. These data suggest a different regulation of Notch1 signaling between gastric cancer and CRC.
authors.affiliation: Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi Hospital; University of Bologna. Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Piazzi
authors.forename: Franco
authors.initials: F
authors.lastname: Bazzoli
authors.forename: Luigi
authors.initials: L
authors.lastname: Ricciardiello
mesh_terms: D002135:Calcium-Binding Proteins; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D011401:Promoter Regions, Genetic; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch