Understanding cancer from its very beginnings is part of the Huntsman Cancer Institute (HCI) mission statement for good reason: it's what our researchers work toward every day and it is critical to the end goal of finding better treatments—and, perhaps a cure. 

Katharine Ullman, PhD, professor in the Department of Oncological Sciences at the University of Utah and co-leader of the Cell Response and Regulation Program at HCI, is one such researcher. Her work identified a quality control mechanism involved in the final step of cell division—called abscission—when the two new cells split apart.

"I like to think in terms of 'how does cancer start,'" says Ullman. "When a cell divides, the two new cells have to completely reform. We’ve identified a step in the cell division process that appears to check if the two new cells have proper reformation of nuclear structure before abscission." This research discovery stemmed from Ullman's interest in the nuclear pore complex and its role in cell division.

"Our previous data led us to ask what would happen to the beginning stages of cell division if we depleted the cells of a particular nuclear pore protein, Nup153," says Ullman. "When we tracked this, we unexpectedly saw under certain conditions that cells were taking a longer time to finish dividing. This intrigued me."


Katharine Ullman, PhD

The nuclear pore complex is made of hundreds of proteins that build a communication channel between the nucleus and the rest of the cell. In addition to their role as transport channels, the pores contribute to nuclear structure and organization.

"Only recently has research looked at the nuclear pore complex as a source of understanding cell cycle regulation," says Ullman. "If the nuclear pore complexes are not rebuilt correctly, this appears to trigger a signal that stops the cell division process."

Ullman used lab-grown cervical cancer cells to test how they would respond when depleted of Nup153 and realized that the cells had a significant delay prior to abscission. "We found that in the absence of Nup153, a set of architectural elements weren’t being put back together correctly during nuclear reformation," Ullman explains. "At the same time, we saw another protein, Aurora B, stopping the cell cycle from proceeding. We hypothesize Aurora B is conveying a quality control signal that ensures the DNA gets packaged into nuclei with the appropriate structure before abscission takes place."


The cells depleted of Nup153 did eventually separate, but Ullman questions if that would happen in a healthy, non-cancerous cell. "Maybe the delay would result in cell death rather than eventual separation—essentially stopping abnormal cells from developing,” says Ullman. "That's something we need to test. Now that we know about this quality control step, we can really ask questions to help us understand steps in cell deregulation that may contribute to the development of cancer."

Identifying this quality control step not only allows further understanding of how cancer begins, but also improving cancer treatments. Aurora B is a target for new chemotherapy drugs because of its role in beginning and ending many steps of cell division.

Douglas R. Mackay, PhD, and Masaki Makise, PhD, both postdoctoral fellows in the Department of Oncological Sciences, co-authored the study that was published in the November 2010 issue of The Journal of Cell Biology. As co-leader of HCI’s Cell Response and Regulation Program, Ullman cultivates collaboration among her department's researchers and throughout HCI. "As a program leader, I enjoy the opportunity to think more broadly about this and other HCI projects," says Ullman, "and to look for ways to create more synergism among the research groups here."

With Ullman and her colleagues nurturing seeds of scientific breakthroughs and collaboration at HCI, understanding how cancer begins, and improved ways to prevent and treat it, are sure to grow.