title: Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene.
abstract: p120-catenin (p120ctn) interacts with E-cadherin, but to our knowledge, no formal proof that p120ctn functions as a bona fide tumor suppressor gene has emerged to date. We report herein that p120ctn loss leads to tumor development in mice. We have generated a conditional knockout model of p120ctn whereby mice develop preneoplastic and neoplastic lesions in the oral cavity, esophagus, and squamous forestomach. Tumor-derived cells secrete granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNFα). The tumors contain significant desmoplasia and immune cell infiltration. Immature myeloid cells comprise a significant percentage of the immune cells present and likely participate in fostering a favorable tumor microenvironment, including the activation of fibroblasts.
authors.affiliation: Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Stairs
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Bayne
authors.forename: Ben
authors.initials: B
authors.lastname: Rhoades
authors.forename: Maria E
authors.initials: ME
authors.lastname: Vega
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Waldron
authors.forename: Jiri
authors.initials: J
authors.lastname: Kalabis
authors.forename: Andres
authors.initials: A
authors.lastname: Klein-Szanto
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Katz
authors.forename: J Alan
authors.initials: JA
authors.lastname: Diehl
authors.forename: Albert B
authors.initials: AB
authors.lastname: Reynolds
authors.forename: Robert H
authors.initials: RH
authors.lastname: Vonderheide
authors.forename: Anil K
authors.initials: AK
authors.lastname: Rustgi
mesh_terms: D000818:Animals; D015820:Cadherins / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000209:etiology*; D051177:Catenins / Q000032:analysis / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000209:etiology*; D005347:Fibroblasts / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D051379:Mice; D009062:Mouth Neoplasms / Q000209:etiology*; D022423:Myeloid Cells / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D016328:NF-kappa B; D000095002:Delta Catenin