title: Loss of desmocollin-2 confers a tumorigenic phenotype to colonic epithelial cells through activation of Akt/β-catenin signaling.
abstract: Desmocollin-2 (Dsc2) and desmoglein-2 (Dsg2) are transmembrane cell adhesion proteins of desmosomes. Reduced expression of Dsc2 has been reported in colorectal carcinomas, suggesting that Dsc2 may play a role in the development and/or progression of colorectal cancer. However, no studies have examined the mechanistic contribution of Dsc2 deficiency to tumorigenesis. Here we report that loss of Dsc2 promotes cell proliferation and enables tumor growth in vivo through the activation of Akt/β-catenin signaling. Inhibition of Akt prevented the increase in β-catenin-dependent transcription and proliferation following Dsc2 knockdown and attenuated the in vivo growth of Dsc2-deficient cells. Taken together, our results provide evidence that loss of Dsc2 contributes to the growth of colorectal cancer cells and highlight a novel mechanism by which the desmosomal cadherins regulate β-catenin signaling.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Keli
authors.initials: K
authors.lastname: Kolegraff
authors.forename: Porfirio
authors.initials: P
authors.lastname: Nava
authors.forename: My N
authors.initials: MN
authors.lastname: Helms
authors.forename: Charles A
authors.initials: CA
authors.lastname: Parkos
authors.forename: Asma
authors.initials: A
authors.lastname: Nusrat
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051187:Desmocollins / Q000172:deficiency / Q000235:genetics; D051301:Desmoglein 2 / Q000235:genetics / Q000378:metabolism; D003896:Desmosomes / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C081561:DSC2 protein, human; D051187:Desmocollins; D051301:Desmoglein 2; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D051176:beta Catenin; D051058:Oncogene Protein v-akt