A UCLA study has identified a way to turn off a key signaling pathway involved in physiological processes that can also stimulate the development of cancer and other diseases. The findings may lead to new treatments and targeted drugs using this approach.
In the study, which is currently available in the online edition of the journal Molecular Endocrinology, scientists found that by activating a receptor in cells called the liver X receptor (LXR), they were able to inhibit the hedgehog (Hh) signaling pathway, which is involved in the maintenance of tissue integrity and stem cell generation. When stimulated in an unregulated manner, however, the Hh pathway can also cause cancers of the brain, lung, blood, prostate, skin and other tissues.
Blocking such unregulated stimulation of the Hh pathway had previously been shown in animal studies to prevent cancers, according to the researchers. How LXR was able to inhibit tumor cell growth by impeding the Hh pathway was previously unknown.
"Our finding shows that activation of LXR signaling is a novel strategy for inhibiting Hh pathway activity and for targeting various cell types, including cancer cells, which may provide important clues as to how we might be able to intervene with tumor formation," said Farhad Parhami, a professor of medicine at the David Geffen School of Medicine at UCLA and the study's principal investigator.
During the study, researchers performed various tests activating LXR receptors in cells and found that specific gene expression induced by the Hh pathway could be inhibited. This finding was also confirmed in mice.
"Since Hh signaling plays a major role in other physiological and pathological processes, we may be able to impact other diseases as well," Parhami said.
Dr. William Matsui of Johns Hopkins Medical Institute, an expert on Hh signaling in cancer development, noted the importance of the UCLA study and its sign
|Contact: Rachel Champeau|
University of California - Los Angeles