Accession Number:

ADA548155

Title:

Mechanisms of Twist 1-Induced Invasion in Breast Cancer Metastasis

Descriptive Note:

Annual summay rept. 1 Jan 2010-31 Dec 2010

Corporate Author:

CALIFORNIA UNIV SAN DIEGO LA JOLLA

Personal Author(s):

Report Date:

2011-01-01

Pagination or Media Count:

47.0

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.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE