UIC Researchers Identify Protein Target to Make Metastatic Cancer Cells Stiffer

The Biophysical Mechanics of Metastasis

The physical composition of a tumor is often deceptive. While the outer shell of a tumor mass can be rigid enough for patients to feel as a distinct lump, the individual cancer cells within are often soft, flexible, and gooey, according to Ekrem Emrah Er, a senior author of the study and assistant professor of physiology and biophysics at the University of Illinois Chicago. This softness is a tactical advantage for the cancer; it allows cells to leak out of the primary tumor, disseminate through the body, and metastasize to distant organs.

When immune cells—specifically T cells and natural killer cells—attempt to destroy these soft cancer cells, the physical resistance is insufficient to trigger a lethal impact. As described by the researchers, the immune cells effectively bounce off them like jelly rather than causing the cell to break apart. The study, published in the journal Developmental Cell, highlights how this biophysical property acts as a shield against the body’s natural defenses.

KCNMB1 as a Druggable Target

To overcome this, researchers sought a way to induce stiffness in cancer cells. The team previously investigated a protein called myocardial-related transcription factor A (MRTFA), which can increase cellular stiffness. However, as Alexa Gajda, the study’s first author and a postdoctoral fellow at the University of Illinois Chicago, noted, MRTFA is a transcription factor and therefore an impractical drug target. Targeting it could trigger unintended downstream effects throughout the cell’s signaling pathways.

By analyzing gene expression patterns, the researchers identified KCNMB1, an ion channel protein that regulates potassium ion movement across membranes, as a key downstream player. Unlike transcription factors, ion channels are well-understood in pharmacology.

Alternative Approaches to Cancer Motility

While the University of Illinois Chicago team focused on cell stiffness, other researchers are exploring different ways to neutralize metastatic movement. A separate study published in Advanced Science by a team including researchers from Penn State University identified the motor protein dynein as critical for cancer cell motility. In this research, blocking dynein prevented breast cancer cells from moving and infiltrating healthy tissues.

Instead of killing the cancer cells with radiation or chemotherapy, we are showing how to paralyze them, said Amir Sheikhi, an assistant professor of chemical engineering and biomedical engineering at Penn State. This approach aims to address the limitations of traditional chemotherapy, which often damages healthy tissue while attempting to eradicate cancer. Although the dynein-targeting research remains in laboratory models—using both two-dimensional collagen fibers and three-dimensional microgel networks—the team views this as a potential strategy to prevent metastasis following the surgical removal of a primary tumor.

The Path Toward Clinical Application

The transition from laboratory findings to clinical practice remains the primary challenge for both the KCNMB1 and dynein research paths. By reversing this effect, the researchers believe they have found a new biophysical front to combat cancer progression.

Patients should consult their healthcare providers regarding current treatment options and clinical trial eligibility, as these findings represent emerging research rather than approved clinical therapies. Further updates on these strategies will depend on the progression of forthcoming animal and human trials.

Sources: Medicalxpress, UIC.