New Strategy Targets Cancer-Specific Protein Links

Researchers at Cornell University have developed a new strategy to identify cancer-specific protein interactions, potentially enabling targeted therapies for prostate, small-cell lung, and pancreatic cancers. By using a photochemically driven labeling technique called “µMap,” the team successfully characterized the c-Myc protein within a cancer-only context, uncovering the signaling protein SLK as a critical co-regulator in disease progression, according to a study published August 13 in Nature Chemical Biology.

Mapping the “Neighborhood” of c-Myc

The research, led by Ciaran Seath, an assistant professor in the Department of Chemistry and Chemical Biology at Cornell, focuses on the c-Myc protein. This transcription factor is deregulated in nearly half of all cancers, driving uncontrolled cellular growth. Because c-Myc is notoriously difficult to target directly, the Cornell team utilized µMap—a nanoscale proximity-labeling method—to visualize the protein’s immediate environment, or “neighborhood,” inside the cell, as reported by Medical Xpress.

“It’s basically a chemistry-based method where you attach a tag, or antenna, onto a protein you’re interested in, and then visualize all of that protein’s interacting partners inside the cell,” Seath said. By attaching these antennas to c-Myc in three distinct prostate cell lines, the researchers mapped the interactomes of healthy cells compared to those with AR-negative and AR-positive prostate cancer.

SLK as a Hidden Cancer Driver

While the study identified several common protein partners, cross-referencing these findings with the DepMap cancer database highlighted SLK as a significant factor in AR-negative prostate cancer. Previously, SLK was largely ignored by the biomedical community because it is present at similar concentrations in both healthy and cancerous cells, according to the Cornell research team.

The discovery lies in the protein’s location rather than its concentration. In cancerous cells, SLK migrates into the nucleus to stabilize c-Myc. “When you have this transcription factor that has maybe 10, 20 or 30 times its regular protein, it can start to go places it shouldn’t and interact with things it shouldn’t,” Seath explained. While healthy cells use nuclear SLK for tissue regeneration, such as healing sunburned skin, cancer cells hijack this mechanism to fuel tumor proliferation.

Future Implications for Targeted Therapy

The ability to distinguish between the “neighborhoods” of proteins in healthy versus diseased cells offers a new handle for drug development. The Seath Lab is currently working to develop therapeutic small molecules that disrupt these novel, cancer-specific complexes. The goal is to create treatments that specifically target the disease while leaving healthy cells unaffected.

This research, supported by the National Institutes of Health, highlights a shift in oncology research toward precision interactome mapping. As the team moves forward, they aim to translate these laboratory discoveries into clinical molecules and potential commercial applications.

Frequently Asked Questions

What is c-Myc and why is it important in cancer?

c-Myc is a transcription factor that controls cellular growth. It is considered a major target in oncology because it is deregulated in nearly 50% of all human cancers.

How does the µMap technique work?

µMap, or MicroMap, is a nanoscale proximity-labeling method that uses chemical antennas attached to a target protein. These antennas allow researchers to visualize and map all the other proteins interacting with the target within the cell.

Why was the SLK protein previously overlooked?

SLK was overlooked because it is expressed at similar levels in both healthy and cancerous cells. Traditional screening methods that look for elevated protein levels failed to identify it as a driver of cancer.

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