MIT News breed · Science

Cellular Pathway Linked to Colorectal Cancer Metastasis Identified

MIT biologists identified a cellular pathway, controlled by YAP1, crucial for colorectal cancer spread. This pathway, normally for tissue repair, is activated by a high-fat diet.

Activated YAP1 promotes cancer cell proliferation and migration. A high-fat diet increases ceramides, which activate YAP1. Drugs blocking ceramide production could prevent metastasis.

While cancer mutations are known, metastasis triggers are not. This study suggests gene activation changes, not new mutations, drive cancer spread.

Using organoids, researchers found metastatic cells activated YAP1. YAP1 normally aids development and regeneration.

Tumor cells hijack this regenerative program, enabling spread. The liver is the most common metastasis site.

High-fat diets increased YAP1 activation in mice. Ceramides release a brake on YAP1, activating metastasis genes.

Targeting YAP1 or ceramide production reduced metastasis in mice. Human data showed higher YAP1 activity in metastatic cells, linked to lower survival.

Researchers plan to develop ceramide-inhibiting drugs. They caution against dietary advice and note ceramides' importance in healthy tissues.

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