LA JOLLA, Calif., July 25, 2011 Metastasisthe spread of cancer from the place where it first started to another place in the bodyis the most common reason that cancer treatments fail. To metastasize, some types of cancer cells rely on invadopodia, cellular membrane projections that act like feet, helping them "walk" away from the primary tumor and invade surrounding tissues. To determine how cells control invadopodia formation, scientists at Sanford-Burnham Medical Research Institute (Sanford-Burnham) screened a collection of pharmacologically active compounds to identify those that either promote or inhibit the process. The study, led by Sara Courtneidge, Ph.D. and postdoctoral researcher Manuela Quintavalle, Ph.D. in collaboration with scientists in Sanford-Burnham's Conrad Prebys Center for Chemical Genomics (Prebys Center), revealed compounds that inhibit invadopodia formation without causing toxicity. The search also turned up several other compounds that increased the number of invadopodia.
Two major findings came out of this research. First, several of the newly identified invadopodia inhibitors targeted a family of enzymes called cyclin-dependent kinases (Cdks), revealing a previously unrecognized role for Cdks in invadopodia formation. Secondly, one of the pro-invadopodia compounds was the chemotherapeutic agent paclitaxela finding that might have implications for the drug's current use in treating cancer. These findings will appear online July 26 in Science Signaling.
"Previous studies by our group and others have demonstrated that we might be able to target invadopodia to prevent cancer cell invasiveness," said Dr. Courtneidge, professor and director of the Tumor Microenvironment Program in Sanford-Burnham's NCI-Designated Cancer Center. "In this study, we established a cell-based screening assay to help us identify regulators of invadopodia formation."
Dr. Courtneidge's group has been studying invadopodia for
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Sanford-Burnham Medical Research Institute