Morphing into Metastasis

Abstract

BIOMEDICINE Epithelial-mesenchymal transitions (EMTs) are processes in which normally immotile epithelial cells are converted into cells that are capable of migrating. Long recognized as a critical step in the tissue remodeling that occurs during animal embryogenesis, EMTs have more recently been implicated in tumor progression and metastasis, events that likewise involve tissue remodeling and cell migration. Exciting new evidence illustrating the importance of EMTs in tumorigenesis is provided by Yang et al. , who report that a transcriptional regulator of embryonic morphogenesis called Twist is required for tumor metastasis in a mouse model of breast cancer. Overexpression of Twist caused tumor epithelial cells to lose their adherent properties, become motile, and express markers of mesenchymal cells: all characteristic features of EMTs. Conversely, suppression of Twist expression by RNA interference produced a marked decline in the numbers of circulating tumor cells and lung metastases in the mice. In support of the clinical relevance of these observations, Twist expression levels in human breast cancer specimens were found to be highest in the most invasive tumors. Further studies of the mechanisms driving EMTs may help identify new drug targets for cancer. — PAK Cell 117 , 927 (2004).