Although the protein-encoding gene p53 has long been tied to cancer cells due to its alteration in nearly every case of cancer, UT Southwestern Medical Center cancer biologists Dr. John Abrams and Dr. Annika Wylie made a profound discovery that links p53 to stem cells. “What this new finding tells us is that an ancient functionality of p53 was hard-wired into stem cell function,” said Dr. Abrams, senior author of the study published in eLife. “From the standpoint of trying to decipher cancer biology, that’s a pretty profound observation.”
It has been well-documented that p53 is an instrumental tumor suppressor by halting the cell cycle when cells are damaged. Yet the gene p53 predates cancer, indicating that the original function was not to stop tumor growth. Working off of evidence from other groups that show p53 is active in stem cells to promote asymmetric division, the UT Southwestern team, which also included Dr. Michael Buszczak, created GFP reporter fruit flies that signaled when certain genes were active in certain cells. After inducing damage via ionizing radiation, the team noticed that p53 activity was restricted to germline stem cells and their immediate progeny. “The discovery was that only the stem cells light up. None of the others do,” explained Dr. Abrams. “The exciting implication is that we are able to understand the function of p53 in stem cells.”
Dr. Abrams explained further why their discovery is so important: “What this new finding tells us is that an ancient functionality of p53 was hard-wired into stem cell function.” Most stem cells in the adult body remain quiescent during times of calm. When damage is present, stem cells divide asymmetrically to yield one stem cell to maintain the stem cell compartment and one differentiated cell to contribute to repair and recovery from the stressor. Stem cells are also hypothesized to play a role in cancer initiation and re-initation. The involvement of stem cells in this study was surprising because, “results suggest that ancient pathways linking p53 to aberrant stem cell proliferation may predate the divergence between vertebrates and invertebrates,” showing that scientists must paint a larger picture to continue to understand the links between p53, tumors, and cancer stem cells.
Findings such as these add prestige to UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center, which is the only National Cancer Institute cancer center in North Texas. UT Southwestern is one of the premier academic medical centers in the nation and integrates pioneering biomedical research with exceptional clinical care and education. Drs. Abrams and Wylie of UT Southwestern were supported by the Cancer Prevention and Research Institute of Texas, the Ellison Foundation, the National Institute of General Medical Sciences, the Welch Foundation, the National Institute of General Medical Sciences, and a Genetic Training Grant.