Activator Protein-1 Activity Regulates Epithelial Tumor Cell Identity

    March 2023
    Michael J. Gerdes, Maxim Myakishev, Nicholas A. Frost, Vikas Rishi, Jaideep Moitra, Abu-Amer Acharya, Michelle R. Levy, Sang‐Won Park, Adam B. Glick, Stuart H. Yuspa, Charles Vinson
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    TLDR Inhibiting AP-1 changes skin tumor types and affects tumor cell identity.
    The study investigated the role of activator protein-1 (AP-1) in skin by using transgenic mice that conditionally express A-FOS, an inhibitor of AP-1. Older mice developed mild alopecia and sebaceous gland hyperplasia. During chemical-induced skin carcinogenesis, inhibiting AP-1 prevented typical squamous lesions and led to benign sebaceous adenomas with H-ras mutations. Inhibiting AP-1 in existing tumors caused squamous tumors to become sebaceous tumors, and reactivating AP-1 reversed this. Tumor cells expressed markers for both lineages, indicating multipotency. AP-1 was found to regulate the balance between wnt/β-catenin and hedgehog pathways, crucial for maintaining squamous tumor identity.
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