Ceramide synthesis mediates colorectal cancer metastasis through a YAP-driven regenerative program.

Ceramide synthesis driven by dietary fat activates YAP signaling, enabling colorectal cancer metastasis independently of primary tumor growth, with 80% of metastases prevented by targeting Basp1.

• Why it matters: Understanding how primary tumor cells gain metastatic ability is crucial for developing targeted therapies, as current knowledge of metabolic and signaling adaptations remains limited.
• What they did: The study used genetic and pharmacological approaches to manipulate ceramide metabolism and YAP activity in colorectal cancer models, focusing on the role of Degs1 and Basp1 in metastasis.
• The result: Blocking ceramide synthesis or Basp1 expression significantly reduced metastasis, revealing ceramide-induced YAP signaling as a key driver of metastatic initiation and a potential therapeutic target.