Other co-authors were Joe Gray, Richard Neve and Debopriya Das of Berkeley Lab's Life Sciences Division.
Cancer and EphA2/ephrin-A1
The term "metastasis" comes from the Greek word for "displacement," and it is used to describe the process whereby cancer cells detach from a tumor, enter the bloodstream and spread to other tissues throughout the body. For example, cancerous breast cells can spread to a lung and form a new breast cancer tumor there. Central to metastasis is the EphA2/ephrin-A1 receptor-ligand complex.
EphA2 is a member of the receptor tyrosine kinase (RTK) family of enzymes that are key regulators of cellular processes. The over-expression of EphA2 has been linked to a number of human cancers, including melanoma, lung, colon and prostate, but is especially prominent in breast cancer. Some 40-percent of all breast cancer patients show an over-abundance of EphA2, with the highest levels found in the most aggressive cancer cells. Ephrin-A1 is a signaling protein that is tethered to the surface of a cell's outer membrane. It binds to EphA2 in a neighboring cell like a key fitted into a lock. When ephrin-A1 binds with EphA2, the newly bound complexes become activated and gather in a cluster.
"The host cell will then literally give the clusters a distinctive tug, applying a force that pulls the clusters across the surface of the cell to a centralized location," Grove says. "What we found is that by applying an opposing force, we could alter the cell's biochemical activity. When we applied a big opposing force we were able to convert able to convert highly invasive cells into well-behaved cells. This shows that in addition to chemically sensing the presence of ephrin-A1, the cells also sense the mechanical properties of the local environment in which ephrin-A1 is displayed."
Observations have indicated that ma
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DOE/Lawrence Berkeley National Laboratory