Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene

Cancer Cell. 2011 Apr 12;19(4):470-83. doi: 10.1016/j.ccr.2011.02.007.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / analysis
  • Carcinoma, Squamous Cell / etiology*
  • Catenins / analysis
  • Catenins / deficiency
  • Catenins / genetics*
  • Catenins / physiology
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Esophageal Neoplasms / etiology*
  • Fibroblasts / physiology
  • Genes, Tumor Suppressor*
  • Humans
  • Inflammation / etiology*
  • Mice
  • Mouth Neoplasms / etiology*
  • Myeloid Cells / physiology
  • NF-kappa B / physiology

Substances

  • Cadherins
  • Catenins
  • NF-kappa B
  • delta catenin

Associated data

  • GEO/GSE20240