ITHACA, N.Y. — A Cornell University-led research team has developed a chemical strategy for mapping the molecular surroundings of one of cancer biology’s most notorious proteins, revealing a previously overlooked partner that may help certain tumors grow. The discovery centers on c-Myc, a transcription factor that regulates genes involved in cell growth and division and becomes dangerously deregulated in nearly half of all cancers. Because c-Myc is essential to many healthy biological processes as well as to tumors, directly blocking it has proved extraordinarily difficult. Rather than attempting to eliminate the protein itself, the researchers looked at the proteins that gather around it in cancer cells, searching for interactions that might be vulnerable to selective treatment.
The study, led by Ciaran Seath, an assistant professor in Cornell’s Department of Chemistry and Chemical Biology, applies a photochemically driven proximity-labeling method known as µMap, or MicroMap. The technique uses chemical “antennas” attached to a protein of interest. When activated by light, those antennas generate reactive species that mark nearby proteins within a nanoscale neighborhood. The labels can then be identified and analyzed, producing an interactome: a map of the protein-to-protein relationships surrounding the target. This approach differs from conventional protein measurements, which generally ask whether a molecule is present at higher or lower levels. µMap instead investigates where a protein is located and which molecular partners it encounters in a particular cellular state.
That distinction was central to the Cornell team’s findings. The researchers attached the labeling chemistry to c-Myc in three prostate cell lines representing healthy prostate cells, androgen receptor-negative prostate cancer and androgen receptor-positive prostate cancer. By comparing the resulting interactomes, they identified proteins that appeared in multiple cellular settings and then used the open-access DepMap cancer database to determine which partners were associated with particular cancer contexts. This cross-referencing highlighted SLK, a signaling protein that had not attracted major attention as a cancer-specific regulator because it is found at broadly similar concentrations in healthy and malignant cells.
The researchers’ subsequent experiments suggested that the critical difference was not how much SLK the cells contained, but where SLK was located. In the cancer context examined in the study, SLK was found in the nucleus, the cellular compartment where DNA is stored and where transcription factors such as c-Myc control gene activity. There, SLK helped stabilize c-Myc, potentially allowing the transcription factor to remain active for longer and sustain the gene-expression programs that support tumor growth. In healthy and cancerous cells alike, the total amount of SLK may appear unremarkable when measured in bulk. Its nuclear localization, however, created a distinct molecular relationship with c-Myc that was associated with disease.
The finding illustrates why cancer research increasingly focuses on cellular context rather than protein abundance alone. A protein that performs a useful function in normal tissue can be repurposed by a tumor without being overproduced. SLK, for example, appears to participate in tissue regeneration. Seath compared this capacity to the repair of sunburned skin, in which cells temporarily activate programs that promote renewal. Cancer cells may co-opt similar regenerative mechanisms, keeping them active inappropriately and using them to drive continued proliferation. By identifying the specific protein complexes formed in malignant cells, researchers may be able to interfere with the tumor’s version of the process while leaving normal repair mechanisms intact.
The work is particularly significant because c-Myc has long been regarded as a compelling but challenging therapeutic target. As a transcription factor, c-Myc does not present the same kinds of deep binding pockets that make many enzymes or cell-surface receptors easier to inhibit with conventional drugs. It also operates at the center of a broad network of normal cellular functions. Directly suppressing it could therefore damage healthy tissue. The Cornell strategy offers a different route: target an accessory interaction that becomes important only when c-Myc is misregulated and operating in a cancer-specific molecular environment. In principle, a drug directed at the SLK–c-Myc relationship could exploit that dependency rather than shutting down c-Myc throughout the body.
Seath said that unusually high levels of c-Myc can cause the protein to move into cellular neighborhoods where it would not normally accumulate and to engage with partners it would not ordinarily encounter. Those abnormal interactions may provide “handles” for therapeutic intervention. The µMap platform is designed to detect precisely these local changes, making it possible to distinguish a protein’s disease-associated neighborhood from its normal one. Such information could be especially valuable in cancers that differ according to their molecular subtype. In this study, the association with SLK was emphasized in androgen receptor-negative prostate cancer, a form of disease that can be difficult to treat because it lacks the receptor targeted by several established hormonal therapies.
The implications may extend beyond prostate cancer. The researchers identified c-Myc as a central driver in a range of aggressive malignancies, including small-cell lung cancer and pancreatic cancer. However, the SLK interaction will need to be tested in additional tumor types, animal models and ultimately human disease before its therapeutic importance can be established. Protein interactions can vary significantly between tissues, genetic backgrounds and stages of cancer, and an interaction that is essential in one tumor subtype may be less important in another. The group’s approach could nevertheless provide a general framework for discovering such context-dependent dependencies, particularly those that remain invisible when researchers examine only total protein levels.
The study, titled “Photoproximity Labeling of c-Myc Reveals SLK as a Cancer-specific Co-regulator,” was published Aug. 13 in Nature Chemical Biology. The Cornell team is now working toward the development of small molecules that could disrupt the cancer-associated signaling relationship. Turning the discovery into a medicine will require solving the usual challenges of drug development, including achieving selectivity, reaching the correct cellular compartment and demonstrating that the treatment is safe in normal tissues. Still, the researchers argue that mapping where cancer proteins operate—and which partners they recruit—could open a new class of precision strategies. Instead of treating a protein as uniformly dangerous or harmless, scientists may be able to target the specific molecular neighborhood in which it becomes an engine of disease.
Subject of Research: Cancer-specific protein interactions involving c-Myc and SLK, with a focus on prostate cancer and potential applications in other aggressive cancers.
Article Title: “Photoproximity Labeling of c-Myc Reveals SLK as a Cancer-specific Co-regulator”
News Publication Date: August 13, 2026
Web References: Nature Chemical Biology article; Cornell Chronicle report; Ciaran Seath laboratory
References: National Institutes of Health support; DepMap cancer database
Keywords: Cancer cells, cancer cell lines, c-Myc, SLK, protein activity, proteins, photoproximity labeling, protein-protein interactions, prostate cancer, precision oncology
Tags: c-Myc protein interactions in cancerchallenges in directly targeting c-Myc in tumorschemical antennas for protein interaction analysisidentifying cancer-specific protein partnerslight-activated protein labeling in cancer researchmapping molecular surroundings of oncogenic proteinsnovel methods for studying cancer cell proteomicsproximity-labeling chemical strategy for tumor protein mappingtargeting protein interactions in cancer therapytumor biology and protein interaction networksµMap technique for cancer protein interactome
