Kinase Shapes Tumor Evolution

One of the biggest challenges in cancer research is figuring out how cells communicate with each other and adjust as tumors grow. A new study in Communications Biology looked at a signaling system called the WNK-OSR1/SPAK kinase pathway. Kinases are proteins that act like

switches inside cells, turning other proteins on or off. The researchers wanted to see what new partners these kinases might interact with, since those interactions could help explain how cancer cells survive and change.

To do this, they searched through about 3,700 short protein sequences, called motifs. Motifs are like small patterns in proteins that help them connect with others, almost like puzzle pieces. The team used computer analysis to score these motifs based on how common they are across species (evolutionary conservation), where they’re located in a cell, and whether they’re easy to reach for interactions. After that, they tested the top candidates in the lab using different techniques that show whether proteins stick together.

https://www.science.org/doi/10.1126/scisignal.2005365 

Through this process, researchers found two new proteins that directly connect with the WNK pathway: Cavin1, which helps shape tiny structures in the cell membrane called caveolae, and TSC22D1, a transcription factor that helps control which genes are turned on or off. The researchers also studied the CCT domains, the parts of the kinase proteins that do the binding, and discovered that they have flexible “pockets” that allow them to connect with many different proteins.

These results show that the WNK-OSR1/SPAK pathway is involved in much more than just moving ions (charged particles) in and out of cells, which was its main known role. It also seems to play a part in cell structure and gene regulation. By combining computer predictions with lab experiments, this study shows a powerful way to uncover hidden networks inside cells—knowledge that could one day help scientists better understand how tumors grow and adapt.

Here is the link to the study: https://www.nature.com/articles/s42003-025-08551-5