A cell-based small molecule screening method for identifying inhibitors of epithelial-mesenchymal transition in carcinoma

PLoS One. 2012;7(3):e33183. doi: 10.1371/journal.pone.0033183. Epub 2012 Mar 14.


Epithelial Mesenchymal Transition (EMT) is a crucial mechanism for carcinoma progression, as it provides routes for in situ carcinoma cells to dissociate and become motile, leading to localized invasion and metastatic spread. Targeting EMT therefore represents an important therapeutic strategy for cancer treatment. The discovery of oncogene addiction in sustaining tumor growth has led to the rapid development of targeted therapeutics. Whilst initially optimized as anti-proliferative agents, it is likely that some of these compounds may inhibit EMT initiation or sustenance, since EMT is also modulated by similar signaling pathways that these compounds were designed to target. We have developed a novel screening assay that can lead to the identification of compounds that can inhibit EMT initiated by growth factor signaling. This assay is designed as a high-content screening assay where both cell growth and cell migration can be analyzed simultaneously via time-course imaging in multi-well plates. Using this assay, we have validated several compounds as viable EMT inhibitors. In particular, we have identified compounds targeting ALK5, MEK, and SRC as potent inhibitors that can interfere with EGF, HGF, and IGF-1 induced EMT signaling. Overall, this EMT screening method provides a foundation for improving the therapeutic value of recently developed compounds in advanced stage carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biological Assay
  • Carcinoma / pathology*
  • Cell Count
  • Cell Line, Tumor
  • Drug Evaluation, Preclinical / methods*
  • Epidermal Growth Factor / pharmacology
  • Epithelial-Mesenchymal Transition / drug effects*
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • Image Processing, Computer-Assisted
  • Inhibitory Concentration 50
  • Insulin-Like Growth Factor I / pharmacology
  • Reproducibility of Results
  • Small Molecule Libraries / analysis*
  • Small Molecule Libraries / pharmacology*


  • Antineoplastic Agents
  • Small Molecule Libraries
  • Epidermal Growth Factor
  • Hepatocyte Growth Factor
  • Insulin-Like Growth Factor I