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    Area of Science:

    • Cancer Biology
    • Cellular Reprogramming
    • Multiomics

    Background:

    • Tumorigenesis begins with normal progenitor cells transitioning to cancer.
    • In vivo observation of early tumor initiation remains challenging.

    Purpose of the Study:

    • To unveil the reprogramming processes of oral epithelial progenitor cells into tumor-initiating cells (TICs) at single-cell resolution.
    • To identify molecular mechanisms and conserved pathways in early oral cancer development.

    Main Methods:

    • Spatiotemporally controlled oncogene activation and tumor suppressor inhibition in vivo.
    • Single-cell resolution multiomics analysis.
    • Investigating YAP-mediated transcriptional networks and cellular signaling.

    Main Results:

    • Identified TICs with a distinct stem-like state characterized by aberrant proliferation, hypoxia, squamous differentiation, and partial epithelial-to-mesenchymal transition (pEMT).
    • YAP activation in TICs promoted oncogenic transcription, mTOR signaling, and myeloid cell recruitment to the invasive front.
    • TIC transcriptional programs are conserved in human head and neck cancers and correlate with poor patient survival.

    Conclusions:

    • Elucidated the single-cell resolution processes of cancer initiation and TIC reprogramming.
    • Highlighted the role of YAP signaling in driving TIC phenotypes and tumor infiltration.
    • Identified conserved TIC programs in head and neck cancer, suggesting potential targets for early detection and prevention.