Snail promotes Cyr61 secretion to prime collective cell migration and form invasive tumor nests in squamous cell carcinoma

Cancer Lett. 2013 Feb 28;329(2):243-52. doi: 10.1016/j.canlet.2012.11.023. Epub 2012 Nov 27.

Abstract

We previously identified genes associated with Snail-mediated squamous cell carcinoma (SCC) invasiveness, in which we observed significant elevation of Cyr61 expression. In this study, SCC cell lines overexpressing Cyr61 exhibited constitutive activation of Rho A and upregulated invasiveness without the disruption of homophilic cell attachment. Humoral Cyr61 enhanced further production of endogenous Cyr61 by SCC cells, which stimulated collective cell migration and the development of an invasive tumor nest. We propose a Cyr61-dependent model for the development of invasive SCC nest, whereby a subset of tumor cells that highly produce Cyr61 may direct other tumor cells to undergo collective cell migration, resulting in a formation of primary SCC mass.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement*
  • Cysteine-Rich Protein 61 / metabolism*
  • Epithelial-Mesenchymal Transition
  • Feedback, Physiological
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Integrins / metabolism
  • Luciferases, Renilla / biosynthesis
  • Luciferases, Renilla / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic
  • Signal Transduction
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*

Substances

  • CCN1 protein, human
  • Cysteine-Rich Protein 61
  • Integrins
  • Snail Family Transcription Factors
  • Transcription Factors
  • Luciferases, Renilla