Some skin cancer may be mediated by primary cili...(irts of the cell primary cilia help dete...)

Date:8/23/2009

irts of the cell, primary cilia help determine which genes are turned on in the nucleus. Two cilia proteins, called Smoothened and Gli, are pivotal in this process. When mutated, they can trigger basal cell carcinoma and other cancers. Clinical trials are already underway to treat cancer with drugs that block the activity of one of these rogue proteins.

"Attacking cilia directly could provide an effective complementary treatment for some cancers," Reiter said, noting that nearly all cancer treatments combine several approaches to kill tumors.

In addition, primary cilia could serve as indicators of the specific mutation causing a cancer, and also help identify how aggressive a tumor is both useful diagnostics to direct treatment, Reiter said.

The experiments in Reiter's lab drew on discoveries that solitary cilia help choreograph the steps needed to shape the developing embryo. A much-studied signaling molecule called Sonic Hedgehog cruises between cells to direct their behavior, and carries instructions to activate sets of genes at different stages of development. Its signal is also essential for normal cell growth. And when the signaling process goes awry, it can trigger cancer.

Six years ago, scientists found that the potent signaling molecule can't function without primary cilia. Then in 2005, Reiter and colleagues discovered that Hedgehog prompts the Smoothened protein to head to the cilium where it knocks out a Gli "repressor," thereby freeing Gli to switch on genes needed for embryo growth.

The new research reveals that removing primary cilia from skin cancer cells blocks the mutated, hyper-active Smoothened from stimulating tumor growth. The study also found that removing primary cilia actually boosts tumor growth spurred by the other mutated protein, Gli.

In other words, cilia promote cancer growth if Smoothened is hyper-active, but they suppress cancer if Gli is hyper-active.

The scientists hypothesize that witho
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Contact: Jennifer O'Brien jobrien@pubaff.ucsf.edu 415-476-2557 University of California - San Francisco Source:Eurekalert

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