Nonadhesive functions of E-cadherin promote cancer cell survival and metastasis.

Deleting E-cadherin in invasive ductal breast cancer cells increases mitochondria-derived ROS, and blocking that ROS rescues cell death and metastasis in vivo.

• Why it matters: E-cadherin is known to suppress invasion yet promote metastasis, but the apoptosis-inducing ROS source and the E-cadherin domains required for survival were unclear.
• What they did: They inhibited mitochondria-derived ROS and tested rescue in 3D colony formation and in vivo metastasis assays after E-cadherin deletion, then used Cdh1 domain mutants to map functional requirements.
• The result: Extracellular-domain deletions, adhesion disruption, or blocked catenin interactions still rescued elevated mitochondrial ROS and 3D colony formation, whereas loss of the cytoplasmic domain failed to rescue ROS or cell death.