Mechanism of Twist1-Induced Invasion in Breast Cancer Metastasis
Annual summary 1 Jan 2009-31 Dec 2011
CALIFORNIA UNIV SAN DIEGO LA JOLLA
Pagination or Media Count:
The transcription factor Twist1 is an important mediator of breast cancer metastasis by driving the epithelial-mesenchymal transition. We find that Twist1 promotes metastasis by inducing the formation of invadopodia, subcellular structures that localize protease activity and secretion to areas of the cell in contact with the basement membrane. Twist1 regulates invadopodia formation by increasing Src kinase activity through upregulation of platelet-derived growth factor PDGF receptors. In addition, Twist1 regulates focal adhesion formation and adhesion through upregulation of a disintegrin and metalloprotease 12 ADAM12. ADAM12 disrupts focal adhesion formation or stability. As focal adhesions antagonize invadopodia formation, this further promotes invadopodia formation, invasion, and metastasis downstream of Twist1.
- Anatomy and Physiology
- Medicine and Medical Research