Researchers at the University of Illinois Chicago have identified a molecular switch, the ion channel protein KCNMB1, that regulates cancer cell stiffness. By activating this pathway, scientists can make metastatic cells more rigid, rendering them vulnerable to destruction by the immune system, according to a study published in the journal Developmental Cell.
The Physics of Metastasis
Cancer cells often evade the immune system by becoming soft and flexible, a trait that allows them to “leak” out of primary tumors and spread to other organs. According to Ekrem Emrah Er, a senior author of the study and assistant professor of physiology and biophysics at the University of Illinois Chicago, these cells possess a counterintuitive physical nature. While the outer shell of a tumor feels rigid to the touch, the individual cells inside remain fluid and gooey.
When immune cells, such as T cells and natural killer cells, attempt to attack these soft cancer cells, they often fail to shatter them. Instead, the cancer cells bend under the pressure, effectively bouncing off the immune response. This physical resilience is a primary driver of metastasis, as identified by researchers at the University of Illinois Cancer Center.
Did you know?
Tumors create potassium-rich environments that can soften cancer cells and suppress immune responses.
Targeting KCNMB1 to Stiffen Cancer Cells
The research team identified the ion channel protein KCNMB1 as the mechanism controlling this cellular stiffness. By modulating the movement of potassium ions across cell membranes, KCNMB1 acts as a switch: reducing its expression makes cells softer, while enhancing its activity makes them stiffer and more susceptible to immune attack.
This discovery improves upon previous research involving the protein MRTFA. While MRTFA also increases cellular stiffness, it is a transcription factor, making it a difficult target for drug development. “It’s not a great drug target, because it’s a transcription factor. If you were to mess with something that high up in a pathway, you can cause a whole bunch of downstream effects that are unintentional,” said Alexa Gajda, the study’s first author and a postdoctoral fellow at UIC.
Therapeutic Potential of Ion Channel Activators
Because ion channels are already common targets for existing medications—such as those used for stroke or cardiovascular disease—the path to clinical application may be more straightforward. The researchers tested a potassium-channel activator known as BMS-204352 in animal models of metastatic breast cancer.
The results showed that the drug effectively reduced distant tumor growth in the lungs by restoring the immune system’s ability to target metastatic cells. This suggests that future cancer therapies could shift toward a biophysical approach, attacking the tumor’s structural integrity to clear the way for the body’s natural defenses.
While this approach is currently in the experimental stage, it highlights the importance of “biophysical fronts” in oncology.
Frequently Asked Questions
Why are metastatic cancer cells softer than healthy cells?
Metastatic cells become soft to remain flexible and “gooey,” which allows them to detach from the primary tumor, enter the bloodstream, and move through the body to colonize new organs.
How does the KCNMB1 protein help the immune system?
KCNMB1 regulates potassium ion movement. By activating this channel, the cell becomes stiffer. This rigidity prevents the cancer cell from bending away from immune attacks, allowing T cells and natural killer cells to effectively destroy them.
Is there a drug currently available for this?
The researchers tested a potassium-channel activator called BMS-204352 in animal models. While this shows promise, further research is required before the treatment can be tested in human patients.
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