Breakthrough Discovery: How Healthy Stem Cells Turn into Oral cancer Stem Cells
Every year, nearly 60,000 people in the U.S.are diagnosed with oral cancer, and the rate of new cases continues to rise, according to the American Cancer Society. Now, researchers at the University of California San Diego have uncovered how healthy stem cells are transformed into cancer stem cells in the earliest stages of the disease. This groundbreaking discovery could pave the way for new treatments and early interventions.
Oral cancer,also known as head and neck squamous cell carcinoma, affects the mouth, throat, nose, sinuses, and voice box. It originates in epithelial cells,the top layer of cells lining these cavities. Approximately 30% of oral cancer cases are linked to the human papillomavirus (HPV).
The researchers discovered that activating a signaling protein called YAP (yes-associated protein) in combination with HPV oncogenes triggered a cascade of cellular and molecular changes. These changes reprogrammed normal stem cells into cancer cells in a mouse model.
Using cutting-edge technologies like cell tracing and multi-omics, the team traced the progression of these changes at the resolution of a single cell. This allowed them to observe the real-time change of healthy stem cells into cancer stem cells in a living organism.
“We can understand precisely how you go from one cell state to another cell state and identify the very, very early events in tumor initiation rather than the final state of cancer,” saeid senior author J. Silvio Gutkind, Ph.D., Distinguished Professor and chair at UC San Diego School of Medicine Department of Pharmacology, and associate director for basic science at UC San Diego Moores Cancer Center.
The study revealed that activating YAP in combination with HPV oncogenes:
- Resulted in invasive cancer within just 10 days;
- Caused a loss of normal cell identity by halting normal cell differentiation, leading to a more mobile and invasive state;
- Promoted unrestrained cell proliferation by stimulating pathways related to carcinoma cell growth, survival, and migration; and
- Resulted in the secretion of factors that recruited and reprogrammed immune cells to break down tissue barriers, evade immune detection, and facilitate tumor cell invasion.
Gutkind’s team is now using the same technologies to study HPV-negative oral cancers, which are most common in smokers and older patients. they are also exploring whether recently developed drugs that block YAP function could provide new treatment options for oral cancers.
One promising candidate is metformin, an inexpensive medication long used to control blood sugar in diabetic patients. A clinical trial is currently underway at UC San Diego to test whether metformin interferes with YAP in patients with oral pre-malignancies.
This research not only deepens our understanding of oral cancer but also opens the door to developing therapeutics that target HPV-positive cancers at their earliest stages.
| Key Findings | Implications |
|——————|——————|
| YAP activation with HPV oncogenes leads to invasive cancer in 10 days | Early detection and intervention strategies |
| Loss of normal cell identity and increased mobility | Potential to halt cancer progression |
| Unrestrained cell proliferation and immune evasion | New therapeutic targets for treatment |
| Metformin as a potential YAP inhibitor | Affordable treatment option for oral cancer |
This discovery marks a significant step forward in the fight against oral cancer, offering hope for more effective treatments and improved patient outcomes.
