Cell structures that move away from their extracellular matrix (the areas outside cells that give them a platform for growth, communication and organization) or attach to the wrong type of matrix are programmed to die, which is a form of apoptosis called anoikis. Steven Frisch, Ph.D. (now with West Virginia University), discovered and named this phenomenon in his laboratory at Sanford-Burnham. When functioning properly, this biological safeguard prevents cells from reattaching and proliferating at inappropriate locations. Unfortunately, metastatic tumor cells have undergone changes that make them resistant to anoikis, permitting them to survive and proliferate elsewhere.

Understanding why anoikis does or does not take place is critical to understanding metastasis. Dr. Frisch’s laboratory and many other labs internationally have been investigating the cell signaling mechanisms that control anoikis.

Cell adhesion-mediated survival signaling is complex, but some of the major players have been identified by these efforts. In particular, in collaboration with Dr. Kristiina Vuori, Dr. Frisch’s laboratory reported a role for focal adhesion kinase (FAK)—a signaling molecule that is over-expressed in numerous human cancers—in cell survival. FAK is thus a potential anti-cancer drug target. In collaboration with the Conrad Prebys Center for Chemical Genomics, Drs. Kristiina Vuori and Nicholas Cosford are working to identify FAK inhibitors that may lead to future cancer therapies.

Downstream of FAK, numerous laboratories have noted an important role for other kinases, called ERKs and Akt, in promoting cell survival. Interactions of FAK with these and other molecules are providing a framework for novel drug discovery efforts focused on restoring anoikis sensitivity in tumor cells.

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Genes and Cancer: Tumor Development
Communications Breakdown: Signal Transduction
Rebuilding Cancer’s Neighborhood: Tumor Microenvironment
Unlocking the Secrets of Cell Death: Apoptosis and Cell Death Research
Breast Cancer