Researchers at UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered a mechanism by which certain adult stem cells suppress their ability to initiate skin cancer during their dormant phase — an understanding that could be exploited for better cancer-prevention strategies.
The study, which was led by UCLA postdoctoral fellow Andrew White and William Lowry, an associate professor of molecular, cell and developmental biology who holds the Maria Rowena Ross Term Chair in Cell Biology in the UCLA College of Letters and Science, was published online Dec. 15 in the journal Nature Cell Biology.
Hair follicle stem cells, the tissue-specific adult stem cells that generate the hair follicles, are also the cells of origin for cutaneous squamous cell carcinoma, a common skin cancer. These stem cells cycle between periods of activation (during which they can grow) and quiescence (when they remain dormant).
Using mouse models, White and Lowry applied known cancer-causing genes to hair follicle stem cells and found that during their dormant phase, the cells could not be made to initiate skin cancer. Once they were in their active period, however, they began growing cancer.
"We found that this tumor suppression via adult stem cell quiescence was mediated by PTEN, a gene important in regulating the cell's response to signaling pathways," White said. "Therefore, stem cell quiescence is a novel form of tumor suppression in hair follicle stem cells, and PTEN must be present for the suppression to work."
Understanding cancer suppression through quiescence could better inform preventative strategies for certain patients, such as organ transplant recipients, who are particularly susceptible to squamous cell carcinoma, and for those taking the drug vemurafenib for melanoma, another type of skin cancer. The study also may reveal parallels between squamous cell carcinoma and other cancers in which stem cells have a quiescent phase.
The research was supported by the California Institute of Regenerative Medicine, the University of California Cancer Research Coordinating Committee and the National Institutes of Health.
The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA's Jonsson Comprehensive Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science.
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Nature Cell Biology