Cancer biologists link tumor suppressor gene to stem cells

Just as archeologists try to decipher ancient tablets to discern their meaning, UT Southwestern Medical Center cancer biologists are working to decode the purpose of an ancient gene considered one of the most important in cancer research.

The p53 gene appears to be involved in signaling other cells instrumental in stopping tumor development. But the p53 gene predates cancer, so scientists are uncertain what its original function is.

In trying to unravel the mystery, Dr. John Abrams, Professor of Cell Biology at UT Southwestern, and his team made a crucial new discovery - tying thep53 gene to stem cells. Specifically, his lab found that when cellular damage is present, the gene is hyperactive in stem cells, but not in other cells. The findings suggest p53's tumor suppression ability may have evolved from its more ancient ability to regulate stem cell growth.

"The discovery was that only the stem cells light up. None of the others do. The exciting implication is that we are able to understand the function ofp53 in stem cells," said Dr. Abrams, Chair of the Genetics and Development program in UT Southwestern's Graduate School of Biomedical Sciences. "We may, in fact, have some important answers for how p53 suppresses tumors."

The findings appear online in the journal eLife, a joint initiative of the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust.

p53 is one of the hardest working and most effective allies in the fight against cancer, said Dr. Abrams. It regulates other genes, marshaling them to carry out an untold number of preemptive attacks and obliterate many pre-cancerous cells before they ever pose a threat. In nearly every case where there's a tumor, p53 is damaged or deranged, strongly suggesting that it is a tumor suppressant.

Stem cells are one of the body's most useful cells because of their regenerative capabilities. Stem cells produce daughter cells, one that is a stem cell and another that can become virtually any kind of cell that's needed, such as a blood cell or a kidney cell. Stem cells have received tremendous attention in cancer research because of the stem cell hypothesis. That hypothesis maintains that malignant tumors are initiated and maintained by a population of tumor cells that have properties similar to adult 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. "From the standpoint of trying to decipher cancer biology, that's a pretty profound observation."

To study the gene, researchers in Dr. Abrams lab, including Dr. Annika Wylie, postdoctoral research fellow and first author on the paper, developed a transgenic sensor that makes cells glow when they are active in drosophila, or fruit flies. Other UT Southwestern researchers involved included Dr. Michael Buszczak, Assistant Professor of Molecular Biology.

The work was 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.

UT Southwestern's Harold C. Simmons Comprehensive Cancer Center is the only National Cancer Institute-designated cancer center in North Texas. The center brings innovative cancer care to the region, while fostering groundbreaking basic research that has the potential to improve patient care and prevention of cancer worldwide.         

About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.