Fox Chase Cancer Center team discovered that two proteins associated with the disease dismantle cilia.

In a 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 what is responsible for dismantling the cell’s antenna.

 “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. comments. Dr. Golemis’ team found that two proteins with important roles in cancer progression and metastasis, HEF1 and Aurora A, play a part in controlling the temporary disappearance of cilia during normal cell division by turning on a third protein, HDAC6. This action causes the cilia to be dismantled in an untimely way.

Dr. Golemis has been studying HEF1 for over a decade, since she first identified the gene. She found that HEF1 has a role in controlling normal cell movement and tumor cell invasion. Dr. Golemis’ laboratory has also shown that Aurora A and HEF1 interact to initiate mitosis during cell division.

In 2006, excessive production of HEF1 (also known as NEDD9) was found to drive metastasis in over one-third of human melanomas, while HEF1 signaling also contributes to glioblastomas, according to the scientists.

Experiments leading to the new research showed that “small-molecule inhibitors of Aurora A and HDAC6 selectively stabilize cilia,” the authors conclude, “suggesting a novel mode of action for these clinical agents.” Clinical trials of such inhibitors have already begun.

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