01Breaking ranks
Epithelial cells are glued together by E-cadherin and sit on a basement membrane. To invade, carcinoma cells often undergo an epithelial–mesenchymal transition (EMT): transcription factors Snail, Slug, Twist and ZEB shut off E-cadherin and turn on mesenchymal markers like N-cadherin and vimentin.
The cells lose polarity, become motile and can squeeze through tissue. Loss of E-cadherin (CDH1) is inherited in hereditary diffuse gastric cancer.
02Clearing a path
Invading cells secrete matrix metalloproteinases (MMPs) that digest the basement membrane and extracellular matrix. They often recruit help — tumor-associated macrophages and fibroblasts secrete growth factors and proteases.
EMT is reversible. After landing in a new organ, cells may undergo MET (mesenchymal–epithelial transition) to grow into a tumor.