Dual cancer role for Daple attracts research team at UC San Diego

Early on in the course of colorectal cancer a protein known as Dishevelled-associating protein with high levels of leucine residues, or Daple, acts as a brake on the cancer. But the same protein, a key coordinator for tissue produced by most cells, becomes a cancer accelerator for late-stage patients, spurring metastasis and speeding the death of patients.

That's the conclusion of a group of investigators at the University of California, San Diego School of Medicine, who are still at work assessing the changing role of Daple in cancer and how that knowledge could be harnessed for new drug development.

"Daple is a double-edged sword," said senior author Dr. Pradipta Ghosh, an associate professor of medicine at UCSD. "The protein is a tumor suppressor early on but heralds faster death in advanced stages of colorectal cancer. We are working to figure out why."

The researchers reached their conclusion after examining tissue samples from 173 stage two colon cancer patients and 51 patients at the stage 4 level. At stage 4 only one in 5 patients in the high-Daple group were alive after 1,000 days. But all patients were alive in the low Daple group.

Daple--which has been the subject of extensive research over the years--works by regulating G proteins, a key cell-signaling protein, and G-protein-coupled receptors play a big role in pharma.

"Our next challenge is to figure out how we can exploit Daple's beneficial attributes while inhibiting its negative ones," Ghosh said.

The study was funded by the National Institutes of Health, the Burroughs Wellcome Fund and the American Cancer Society. The study appears in the June 30 issue of eLife.

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