Mechanism of Twist1-Induced Invasion in Breast Cancer Metastasis.

摘要

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.