A possible new therapeutic avenue may have been opened up with scientific evidence for a never-seen-before way in which cells can sense and respond to physical forces. A team of researchers has shown that the biochemical activity of a cellular protein system, which plays a key role in cancer metastasis, can be altered by the application of a direct physical force. This discovery sheds important new light on how the protein signaling complex known as EphA2/ephrin-A1 contributes to the initiation, growth, and progression of cancerous cells, and also suggests how the activity of cancer cells can be affected by surrounding tissue. 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,” Dr. Groves said. “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 highly invasive cells into well-behaved cells.
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