A recent study has discovered how an anticancer medication initiates a signal from the outside of a cancer cell, allowing the drug to enter the cell. This research, released on January 29 in Nature Communications, highlights a novel signaling pathway that could potentially be used to deliver other pharmaceuticals.
A recent study has discovered how an anticancer medication initiates a signal from the outside of a cancer cell, allowing the drug to enter the cell. This research, released on January 29 in Nature Communications, highlights a novel signaling pathway that could potentially be used to deliver other pharmaceuticals.
Many aggressive cancers produce an excessive amount of a protein called P-cadherin that resides in the cell membrane. Due to the abundant presence of P-cadherin on their surfaces, it has become a target for drug development.
Monoclonal antibodies designed to target P-cadherin can transport drug packages directly to cancer cells. However, the specific mechanism by which these antibodies bind to P-cadherin and facilitate entry into the cancer cell has not been fully understood.
A team of researchers, including graduate students Bin Xie and Shipeng Xu from biophysics and biomedical engineering at the University of California, Davis, along with Professor Sanjeevi Sivasankar, conducted a series of experiments to closely examine how the antibody CQY684 interacts with P-cadherin.
P-cadherin exists in the cell membrane as a dimer, which is a pair formed with the P-cadherin from a neighboring cell. This dimer can take on two shapes: a loose “strand-swap” configuration or a cross-shaped “X-dimer.”
The researchers discovered that when the anticancer antibody attaches to P-cadherin, it stabilizes the protein in the X-dimer formation. This stable configuration activates a signaling process that causes a section of the cell membrane to pinch off, allowing the dimer to enter the cell as a small vesicle. This entire complex of P-cadherin, antibody, and drug is then directed to a part of the cell known as the lysosome for breakdown.
“Our findings establish an outside-in signaling mechanism that offers essential insights into how cells control adhesion,” the authors stated. Gaining an understanding of how antibodies target cadherin could lead to the development of drugs that utilize this method to locate and eliminate cancer cells.
