Scientists discover surprising way cancer may thrive and spread
Cancer cells do not just burn fuel to survive. New research suggests they use that fuel to rewrite the rules of how their own proteins behave, opening a previously hidden front in the fight against the disease.
“Cancer can wear down the immune system’s T cells, making them less effective at attacking tumors,” Ekaterina Vinogradova, head of the laboratory of chemical immunology and proteomics at Rockefeller University, told Newsweek. “Using chemical proteomic approaches, we created the first comprehensive map showing how changes in a cell’s energy-producing molecules affect the proteins that control T cell activity.
“The findings reveal potential new targets for developing effective cancer immunotherapies.”
The work is part of a broader collaboration between Vinogradova and Kivanç Birsoy, head of Rockefeller’s laboratory of metabolic regulation and genetics. Together, the two labs are mapping how cancer cells’ altered metabolism changes the shape and function of proteins throughout the cell, not just how much energy those cells produce.
Every cell breaks down nutrients to generate energy and building blocks. Cancer cells, though, rewire this process extensively to grow faster and survive in hostile conditions. Scientists have increasingly found that the small molecules produced during metabolism, known as metabolites, can directly control how proteins work. But exactly how this happens inside cancer cells has remained poorly understood.
Vinogradova and Birsoy set out to close that gap by combining their separate specialties.
Birsoy’s team studies how metabolic pathways drive tumor growth and spread, and has built tools to examine metabolism inside specific parts of the cell, including the mitochondria, lysosomes and Golgi apparatus. Vinogradova’s lab has developed mass spectrometry techniques that track chemical changes across thousands of proteins at once, revealing shifts caused by oxidation, structural changes and altered interactions with other molecules.
A Discovery About the Cell’s Protein Factory
The collaboration began by studying oxidative stress, but the team soon realized its tools could do more: they could also track how metabolites bind directly to proteins across the entire proteome. That discovery pushed the researchers to start building a full atlas showing how individual metabolites affect protein behavior, a reference map that could help distinguish different causes of protein changes in cancer.
Their first major finding centered on the endoplasmic reticulum, the cellular structure where proteins are built and folded. The team discovered that a protein called SLC33A1 helps keep the endoplasmic reticulum in balance by removing a molecule called oxidized glutathione when levels climb too high.
Dr. Brian Honeyman, a clinical adviser at Marietta Springs, a treatment center in Georgia, who was not involved in the study, told Newsweek that SLC33A1 acts as “one important cell level pressure release valve.”
He explained that losing SLC33A1 causes oxidized glutathione to build up in the endoplasmic reticulum, damaging protein-folding enzymes and forcing the cell to lean harder on its quality-control systems.
“The key finding is that metabolism is not just about supplying energy to cancer cells but also about changing the chemical state of proteins through metabolite changes,” Honeyman said. “This provides a more specific link between abnormal metabolic states and cellular behavior for cancer research.”
A Possible Target for Pancreatic Cancer
The team is now applying its tools to pancreatic cancer, a disease with few effective treatments.
Because pancreatic cancer cells tend to carry high levels of antioxidants such as glutathione, Birsoy said SLC33A1 could be a promising drug target.
Honeyman cautioned that the findings are not yet proof of a treatment. The study did not show that boosting SLC33A1 shrinks tumors, blocks the spread of cancer or improves survival in humans.
“I view this as a mapping of previously unknown cellular circuitry, rather than a direct new therapy,” he said, adding that the work still shows how a metabolic imbalance can ripple into the protein-folding machinery, creating openings for future treatments.
Reference
Vinogradova, E. V., et al. (2026). A post-translational regulatory map of chronic antigen-driven human T cell dysfunction. https://doi.org/10.64898/2026.03.04.709614.
Contact Newsweek editors on this story: Kara Dolman and Emma Lee-Sang
