Investigators at UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered how tissue-specific hair follicle stem cells promote the development of squamous cell skin cancer. They note that understanding the mechanism of stem cell cancer suppression could lead to the development of preventive measures for individuals susceptible to squamous skin cancer. The study was published online on December 15 in the journal Nature Cell Biology.
The research team was led by Andrew White, post-doctoral fellow, and William Lowry, associate professor of molecular, cell and developmental biology in the life sciences and the Maria Rowena Ross Term Chair in Cell Biology. The investigators have found a mechanism in adult stem cells whereby the cells suppress their ability to initiate cancer during their dormant phase; thus, this understanding could evolve into better cancer prevention strategies. Hair follicle stem cells (HFSCs) are the tissue-specific adult stem cells, which generate the hair follicles; they are also the cells of origin for cutaneous squamous cell carcinoma (SCC), which is a common skin cancer. These HFSCs cycle between periods of activation, during which they can grow, and dormancy, when they are inactive.
The researchers used a mouse model in which they applied known cancer-causing genes (oncogenes) to HFSCs; they found that during the cell quiescence phase, the cells could not be made to initiate SCC. However, once the HFSC were in their active period, they began growing cancer. Dr. White explained, “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; 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.”
The investigators note that understanding cancer suppression through quiescence could provide the development better of preventative strategies in patients susceptible to SCC (e.g., organ transplant patients, or those taking the drug vemurafenib for melanoma, another type of skin cancer). This findings of this study might also be helpful for preventing other cancers in which stem cells have a quiescent phase.
This research was supported by the California Institute of Regenerative Medicine (CIRM), University of California Cancer Research Coordinating Committee (CRCC) and National institutes of Health (NIH).