title: Reelin-Dab1 signaling system in human colorectal cancer.
abstract: Reelin is an extracellular matrix protein that plays a critical role in neuronal migration. Here we show that the mucosa of human colon expresses reelin, its receptors ApoER2 and VLDLR, and its effector protein Dab1. Immunohistochemical analyses reveal that reelin expression is restricted to pericryptal myofibroblasts; Dab1 is detected at myofibroblasts, the apical domain of surface epithelial and crypt cells, and a strong linear staining is observed at the basement membrane; VLDLR and ApoER2 are in the cytoplasm of surface epithelium and myofibroblasts, and VLDLR is also detected in the cytoplasm of the crypt cells. Human colorectal cancer downregulates reelin without change in vimentin or N-cadherin mRNA levels. Decreased Reelin mRNA expression is accompanied by decreased HIC1 mRNA levels, increased mRNA levels of ApoER2 and DNMT1, increased reelin hypermethylation and no change in either Cask or TGF-β1 mRNAs, suggesting that reelin repression results from a DNMT1-mediated hypermethylation of the reelin gene promoter. Decreased HIC1 expression may repress reelin transcription via increasing ApoER2 transcription. We conclude that the mucosa of human colon expresses the reelin-Dab1 signaling system and that reelin is repressed in colorectal cancer before epithelial-mesenchymal transition has occurred. The significant down-regulation of reelin expression makes this gene a promising biomarker for colorectal cancers. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Serrano-Morales
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Vázquez-Carretero
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Peral
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Anunciacion Ana
authors.initials: AA
authors.lastname: Ilundáin
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: García-Miranda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D026502:LDL-Receptor Related Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012007:Rectum / Q000378:metabolism / Q000473:pathology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; C115785:DAB1 protein, human; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717127:RELN protein, human; D012697:Serine Endopeptidases
keywords: ApoER2; adenocarcinoma; cancer; colon; reelin