Colorectal Cancer Co-opts an Epidermal Wound Healing Program During Metastasis to Generate Disseminated Tumor Cells

    July 2026 in “ Nature Communications ”
    Mizuho Sakahara, Takuya Okamoto, Kohei Kumegawa, Yasuko Natsume, Daisuke Kusama, Hitomi Yamanaka, Rie Komatsuzaki, Katsuyuki Yaginuma, Upasna Srivastava, Atsushi Takahashi‐Kanemitsu, Etsuo A. Susaki, Kazutaka Obama, Satoshi Nagayama, Reo Maruyama, Ryoji Yao
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    TLDR Colorectal cancer uses wound-healing processes to spread, suggesting new treatment targets.
    The study reveals that colorectal cancer (CRC) cells temporarily adopt an epidermal wound-healing program to facilitate metastasis, characterized by the expression of keratins like KRT17 and KRT6A. This transition involves reduced EZH2 activity and activation of YAP signaling, allowing CRC cells to mimic wound healing processes and enhance their metastatic potential. The research utilized organoids and mouse models, showing that pharmacological activation of YAP and inhibition of EZH2 increased the expression of wound-inducible keratins, promoting dissemination. These findings suggest that targeting the YAP and EZH2 pathways could offer new therapeutic strategies for CRC metastasis.
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