Activator Protein-1 Activity Regulates Epithelial Tumor Cell Identity

August 2006 in “ Cancer Research ”

Michael J. Gerdes, Maxim V. Myakishev, Nicholas A. Frost, Vikas Rishi, Jaideep Moitra, Asha Acharya, Michelle R. Levy, Sang‐Won Park, Adam B. Glick, Stuart H. Yuspa, Charles Vinson

alopecia sebaceous gland hyperplasia AP-1 activator protein-1 A-FOS H-ras mutations wnt/β-catenin signaling hedgehog signaling c-Jun

TLDR AP-1 controls tumor cell type by affecting key signaling pathways.

The study investigated the role of activator protein-1 (AP-1) in regulating epithelial tumor cell identity using transgenic mice. By inhibiting AP-1 through A-FOS expression, researchers observed that older mice developed mild alopecia and sebaceous gland hyperplasia. During chemical-induced skin carcinogenesis, inhibiting AP-1 prevented the development of typical squamous lesions, leading instead to benign sebaceous adenomas with H-ras mutations. Inhibition of AP-1 after tumor formation caused squamous tumors to transdifferentiate into sebaceous tumors, and reactivating AP-1 reversed this process. This transdifferentiation involved cells expressing markers for both lineages, indicating their multipotency. The study highlighted that AP-1 regulates the balance between wnt/β-catenin and hedgehog signaling pathways, crucial for maintaining squamous tumor cell identity, with c-Jun binding to wnt promoters as a key mechanism.

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