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0This research reveals that colorectal cancer (CRC) cells facilitate metastasis by temporarily adopting a wound-healing program typically used by skin cells. By utilizing patient-derived organoids and serial transplantation in mice, scientists identified a rare population of disseminated tumor cells (DTCs) that shed their intestinal identity to express keratins like KRT17. This transition is driven by a combination of reduced EZH2 activity and activated YAP signaling, allowing cancer clusters to survive during travel to distant organs like the liver. The study demonstrates that this lineage plasticity is reversible, as the cells eventually regain their primary tumor characteristics to form mature metastatic growths. These findings highlight a transient and targetable cellular state that is essential for the spread of colorectal cancer. Clinically, the presence of these KRT17+ cells at the invasive edge of tumors may serve as a critical marker for metastatic potential.
References:
Sakahara M, Okamoto T, Kumegawa K, et al. Colorectal cancer co-opts an epidermal wound healing program during metastasis to generate disseminated tumor cells[J]. Nature Communications, 2026.
