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Loss of cell's 'antenna' linked to cancer's development

Submarines have periscopes. Insects have antennae. And increasingly, biologists are finding that most normal vertebrate cells have cilia, small hair-like structures that protrude like antennae into the surrounding environment to detect signals that control cell growth. In a new study published in the June 29 issue of Cell, Fox Chase Cancer Center researchers describe the strong link between ciliary signaling and cancer and identify the rogue engineers responsible for dismantling the cells antenna.

Cilia-based sensing has important roles in sight, smell and motion detection and in helping an embryo develop into a normal baby. Defects in cilia can produce a range of disorders, including kidney cysts, infertility, respiratory problems, reversal of organs (for example, heart on the right) and a predisposition to obesity, diabetes and high blood pressure. In each case, cells fail to appropriately detect growth-controlling signals and develop abnormally. Now, researchers are adding cancer to this list.

Many cancers arise from defects in cellular signaling systems, and we think we have just identified a really exciting signaling connection, Fox Chase Cancer Center molecular biologist Erica A. Golemis, Ph.D., points out. In the new study, Golemis and her Fox Chase colleagues found that two proteins with important roles in cancer progression and metastasis, HEF1 and Aurora A, have an unexpected role in controlling the temporary disappearance of cilia during normal cell division, by turning on a third protein, HDAC6. This action causes the antenna to be dismantled in an untimely way.

Why cilia come and go on normal cells is not entirely understood, but scientists increasingly suspect that it may play a role in timing the cell division process. Commonly, cancer cells have entirely lost their cilia, and this absence may help explain why tumors fail to respond properly to environmental cues that cause normal cells to stop growing. Hence
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Contact: Karen Mallet
Karen.Mallet@fccc.edu
215-728-2700
Fox Chase Cancer Center
28-Jun-2007


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