A new study reveals a groundbreaking mechanism by which an anticancer antibody, CQY684, utilizes a conformational change in the P-cadherin protein to trigger an 'outside-in' signaling pathway. This unique process effectively guides the antibody and its attached drug payload into cancer cells, offering a promising avenue for targeted cancer therapy.
A new study published in Nature Communications on January 29th reveals a novel signaling mechanism that could revolutionize drug delivery to cancer cells. The research, conducted by graduate students Bin Xie and Shipeng Xu, along with Professor Sanjeevi Sivasankar at the University of California, Davis, focuses on the interaction of an anticancer drug with P-cadherin, a protein often overexpressed in malignant cancers.
P-cadherin, embedded in the cell membrane, has attracted attention as a potential target for drug development due to its abundance on the surface of cancer cells. Monoclonal antibodies targeting P-cadherin can be used to deliver drugs directly to these cells. However, the precise mechanism by which these antibodies attach to P-cadherin and subsequently enter the cancer cell remained unclear.Through a series of experiments, the researchers discovered that binding of the anti-cancer antibody CQY684 to P-cadherin triggers a conformational change, locking it into a stable, cross-shaped dimer known as the X-dimer. This stable X-dimer form initiates a chemical signal that causes the surrounding cell membrane to be pinched off, effectively engulfing the antibody-P-cadherin complex within the cell as a tiny vesicle. The entire complex is then transported to a cellular structure called the lysosome for degradation. This finding reveals a previously unknown 'outside-in' signaling pathway, shedding light on how cells regulate adhesion. The research team believes that understanding the binding targets for antibodies against cadherin could pave the way for designing more effective drugs that exploit this pathway to specifically target and destroy cancer cells
Anticancer Drug P-Cadherin Antibody Cancer Therapy Signaling Pathway
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