University researchers have melded their own experiments with a survey of scientific literature to conceive an unexpected hypothesis — a group of proteins previously overlooked in disease research may play a critical role in the growth of ovarian cancer tumors.
The team found that cells churn out templates for one of the proteins — TAF2 — at a higher level in 73 percent of the serious ovarian carcinomas they analyzed from a cancer database. They also noted that the production of another TAF protein increased in 66 percent of the cases they examined.
TAF proteins are “a new type of molecule that may have a very specific effect in these ovarian cancer cells,” said Alex Brodsky, assistant professor of medical science, who was not involved in the study. “In ovarian cancer there needs to be fresh ideas” like this one, he added.
The study was published online in the journal Frontiers in Oncology earlier this month.
Such a novel approach will pave the way for future research on the specifics of the pathways involving these TAF proteins, as well as research on how they can be inhibited, said study co-author Richard Freiman, associate professor of medical science.
Tackling the ‘silent killer’
Nearly 22,000 American women are diagnosed with ovarian cancer annually, and more than 14,000 women die from it each year, according to the American Cancer Society’s website. Despite the large number of patients, there has been little advancement in developing a cure over the last 40 years, Freiman said.
“One of the major issues with ovarian cancer is that there isn’t a ton of research being done about it, and it is a really challenging disease,” said Jennifer Ribeiro GS, who led the study.
The disease is so hard to address because “in terms of genetics, there’s a lot of different sorts of causes of ovarian cancer,” Freiman said. And surgeries and drugs doctors currently prescribe for treatment tend to work only in a small subset of patients, he added.
The disease’s “very subtle” initial symptoms are another factor making it hard for doctors to catch ovarian cancer before it progresses to dangerous levels, Freiman said, noting that some people refer to the disease as “a silent killer.”
“We believe that we need a really novel approach for looking at the disease,” Ribeiro said, adding that analysis of the TAF proteins may provide such a strategy and is worth future examination.
The TAF system is likely not the culprit in all cases of ovarian cancer. But understanding many different mechanisms implicated in the disease could allow scientists to eventually create a battery of treatments encompassing a large proportion of cases, Freiman said, adding that he hopes his work contributes to this goal.
An unexpected start
Ribeiro and Freiman each began looking at TAF proteins in graduate school to investigate the reproductive system of mice.
The group of proteins is key for fertility in female mice, Freiman said, adding that previous experiments have shown mice cannot make viable eggs without it.
The “crossover between a lot of developmental pathways and cancer pathways” led the group of researchers to switch gears and begin looking at the protein’s implications in ovarian cancer, Ribeiro said.
The link between development and cancer is logical — in early stages of development, cells should multiply at a high rate to sustain growth. But if this rapid growth system goes haywire later in life, it can lead to the multiplication of cells, which causes tumors to form.
High levels of a certain TAF protein are associated with the proliferation of ovarian cells necessary to support egg growth, Ribeiro sad. But “expression of a certain TAF goes down as stem cells differentiate.”
This developmental pathway supports the potential role of TAF in ovarian tumor growth because “dedifferentiated tumors are more aggressive or more advanced” than differentiated ones, Ribeiro said.
Another insight that led the researchers to link these proteins with ovarian cancer is that estrogen — a hormone involved in egg maturation in the ovary — causes an increase in the expression of one of the TAF proteins.
Previous studies suggest that women who undergo estrogen therapy have an increased risk of developing ovarian cancer, Ribeiro said.
The next steps
The study’s authors plan to begin researching how TAF proteins can be inhibited by testing different factors on well-established lines of cells derived from ovarian tumors, Ribeiro said. Freiman said he and his colleagues have identified some small molecules that may work as inhibitors.
“These are not the kind of proteins that you would have expected to be important,” Brodsky said. To test their importance, the researchers will need to examine their role in cancer cells from multiple types of tumors, he added.
The link the researchers made to human mutation data “provides evidence that there is really something going on,” but more research is needed to establish a strong connection between the TAF proteins and ovarian cancer, he added.
Due to an editing error, a previous version of this article incorrectly attributed information. Richard Freiman, not Jennifer Ribeiro, said he and his colleagues have identified some small molecules that may work as inhibitors of TAF proteins. The Herald regrets the error.
ADVERTISEMENT
