The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines

Sylvia Julien Grille, Alfonso Bellacosa, John Upson, Andres J. Klein-Szanto, Frans Van Roy, Whaseon Lee-Kwon, Mark Donowitz, Philip N. Tsichlis, Lionel Larue

Research output: Contribution to journalArticle

Abstract

Epithelial-mesenchymal transition (EMT) is an important process during development and oncogenesis by which epithelial cells acquire fibroblast-like properties and show reduced intercellular adhesion and increased motility. Squamous cell carcinoma lines engineered to express constitutively active Akt underwent EMT, characterized by down-regulation of the epithelial markers desmoplakin, E-cadherin, and β-catenin and up-regulation of the mesenchymal marker vimentin. The cells lost epithelial cell morphology and acquired fibroblast-like properties. Additionally, E-cadherin was down-regulated transcriptionally. The cells expressing constitutively active Akt exhibited reduced cell-cell adhesion, increased motility on fibronectin-coated surfaces, and increased invasiveness in animals. AKT is activated in many human carcinomas, and the AKT-driven EMT may confer the motility required for tissue invasion and metastasis. These findings suggest that future therapies based on AKT inhibition may complement conventional treatments by controlling tumor cell invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)2172-2178
Number of pages7
JournalCancer Research
Volume63
Issue number9
StatePublished - May 1 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Grille, S. J., Bellacosa, A., Upson, J., Klein-Szanto, A. J., Van Roy, F., Lee-Kwon, W., Donowitz, M., Tsichlis, P. N., & Larue, L. (2003). The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Research, 63(9), 2172-2178.