Mechanisms of Twist 1-Induced Invasion in Breast Cancer Metastasis

Abstract

Here we identify a novel role for PDGFR-alpha as an essential downstream target of the transcription factor Twist1 for metastasis and local invasion. Twist1 induces the formation of structures called invadopodia that concentrate protease activity to areas of the cell in contact with the extracellular matrix. Twist1-induced invasion and metastasis are dependent on invadopodia formation, as knockdown of an essential invadopodia protein, Tks5, reduces invasion and metastasis. Twist1 induces invadopodia formation by directly inducing transcription of the tyrosine kinase receptor PDGFR-alpha. Upregulation of PDGFR-alpha is necessary for an increase in Src activation observed upon expression of Twist1 in human mammary epithelial cells. Knockdown of PDGFR-alpha reduces both in vitro and in vivo invasion and metastasis. In addition, we identify Twist1 and PDGFR-alpha as markers of poor survival in breast cancer patient populations.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2011
Accession Number
ADA548155

Entities

People

  • Mark Eckert

Organizations

  • University of California, San Diego

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cell Line
  • Cell Movement
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Culture Media
  • Data Sets
  • Department Of Defense
  • Embryos
  • Epithelial Cells
  • Gene Expression
  • Growth Factors
  • Mammary Glands
  • Neoplasms
  • Peptide Growth Factors
  • Three Dimensional

Readers

  • Molecular Biology and Genetics