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The American Cancer Society reports that almost 60,000 people are diagnosed with oral cancer annually, and the number of new cases is steadily increasing. The process by which normal stem cells turn into cancer stem cells during the early phases of the disease has recently been uncovered by scientists from the University of California, San Diego.
The mouth, throat, nose, sinuses, and voice box are all potential sites for oral cancer, which is also called head and neck squamous cell carcinoma. Epithelial cells, which make up the outermost layer of cells lining these areas, are where the cancer begins to develop. Approximately 30% of oral cancers are caused by human papillomavirus or HPV.
Through the activation of a signaling protein known as YAP, which is typically involved in stem cell maintenance and growth, along with HPV oncogenes, a series of cellular and molecular changes were set in motion, causing normal stem cells to be altered into cancer cells in a mouse model.
At the single cell level, the researchers tracked the course of alterations that transformed healthy stem cells into cancer stem cells using many cutting-edge technologies.
Using technologies like cell tracing and multi-omics, this study is the first to track the real-time development of mutations in a living organism. Cell tracing involves marking cells to follow their proliferation through time, while multi-omics analyzes molecular data from genomics, RNA transcription, protein expression, epigenetic changes, and cellular metabolites to understand disease development. The resolution of the study is single cells.
Researchers can recognize exactly how you get from one cell state to another and pinpoint the earliest phases of tumor development as opposed to the final stage of cancer.
When YAP was activated together with HPV oncogenes, the researchers discovered: that within ten days, the cancer became invasive; led to a more mobile and invasive state by preventing normal cell differentiation, resulting in a loss of normal cell identity; enabled unchecked cell proliferation through enhancing epigenetic modifications and activating pathways associated with the development, survival, and migration of cancer cells; and caused the release of substances that attracted and changed immune cells to degrade tissue barriers, avoid immune detection, and promote the invasion of tumor cells.
The next step is to apply these similar technologies to the question of how HPV-negative oral cancers, which predominantly affect smokers and the elderly, evolve from normal stem cells to cancer stem cells. Additionally, the researchers are investigating whether newly created medications that inhibit YAP function could offer novel approaches to treating oral malignancies. The research opens the door to treatments that can detect HPV-positive malignancies in their early stages.
Sources:
Faraji, F., Ramirez, S.I., Clubb, L.M. et al. YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution. Nat Commun 16, 498 (2025). https://doi.org/10.1038/s41467-024-55660-6
https://today.ucsd.edu/story/how-healthy-stem-cells-turn-into-oral-cancer
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AI Disclosure Statement:
The Chromoscience uses AI-assisted tools to support the preparation and editing of science articles. Content is reviewed by the editor for clarity and consistency with the cited research before publication. Readers are encouraged to consult the original scientific publications for complete findings, methods, and limitations.
