title: Unimpaired skin carcinogenesis in Desmoglein 3 knockout mice.
abstract: The contribution of adherens junction inactivation, typically by downregulation or mutation of the transmembrane core component E-cadherin, to cancer progression is well recognized. In contrast, the role of the desmosomal cadherin components of the related cell-cell adhesion junction, the desmosome, in cancer development has not been well explored. Here, we use mouse models to probe the functional role of desmosomal cadherins in carcinogenesis. Because mice lacking the desmosomal cadherin Desmoglein 3 (Dsg3) have revealed a crucial role for Dsg3 in cell-cell adhesion in stratified epithelia, we investigate the consequence of Dsg3 loss in two models of skin carcinogenesis. First, using Dsg3-/- keratinocytes, we show that these cells display adhesion defects in vitro and compromised tumor growth in allograft assays, suggesting that Dsg3 enables tumor formation in certain settings. In contrast, using an autochthonous model for SCC development in response to chronic UVB treatment, we discover a surprising lack of enhanced tumorigenesis in Dsg3-/- mice relative to controls, unlike mice lacking the desmosomal component Perp. Accordingly, there is no defect in the apoptotic response to UVB or enhanced immune cell infiltration upon Dsg3 loss that could promote tumorigenesis. Thus, Dsg3 does not display a clear function as a tumor suppressor in these mouse skin cancer models. Continued unraveling of the roles of Dsg3 and other desmosomal constituents in carcinogenesis in different contexts will be important for ultimately improving cancer diagnosis, prognostication, and treatment.
authors.affiliation: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Baron
authors.forename: Anabel
authors.initials: A
authors.lastname: Hoang
authors.forename: Hannes
authors.initials: H
authors.lastname: Vogel
authors.forename: Laura D
authors.initials: LD
authors.lastname: Attardi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D002448:Cell Adhesion / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000528:radiation effects; D051184:Desmoglein 3 / Q000235:genetics / Q000378:metabolism; D003896:Desmosomes / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014466:Ultraviolet Rays
chemical_list: D051184:Desmoglein 3; C495300:Dsg3 protein, mouse; D008565:Membrane Proteins; C406964:Perp protein, mouse