Protein modifications drive lung cancer resistance
Key protein modifications such as glycosylation and phosphorylation regulate a variety of cellular processes, such as cell-cell recognition, immune response and cell growth. Dysregulation of these tags is linked to human diseases, making them important to study disease progression and identify biomarkers and druggable targets using mass spectrometry. However, since these modifications are often low-abundance and dynamically modified, they need to be enriched first. Despite the progress in the development of individual enrichment strategies, scientists have yet to develop a highly sensitive and robust platform to focus on multiple modifications simultaneously.
Yu-Ju Chen’s team from Taiwan published an in the Molecular & Cellular Proteomics introducing a streamlined enrichment strategy called Fe-ZIC-cHILIC, which captures both glycopeptides, or GPs, and phosphopeptides, or PPs, in a single step. This method uses a tandem tip that is packed with a special material combining iron ions with ZIC-cHILIC resin. In this setup, the sample flows through this tandem tip, minimizing protein loss and enriching GPs in the top tip while PPs are in the bottom tip. Using this strategy, they analyzed nonsmall cell lung cancer cells, or NSCLC cells with mutations in the EGFR gene, which is the first-line targeted therapy yet eventually drives drug resistance and leads to tumor recurrence. Within a single cell type, they identified 10,536 GPs and 11,329 PPs and found significant changes on the site-specific glycopeptides and phosphoptpides between drug-sensitive and drug-resistant cells. Notably, they observed changes in EGFR, ERBB2, MET and integrin family proteins, which are primary targets for cancer treatments.
This study highlights both the novelty of Fe-ZIC-cHILIC material in dual enrichment with high specificity to study protein modifications. Further investigations will assess the strategy in different sample types to determine how these modifications drive resistance and how therapies could be developed to improve outcomes.
Enjoy reading ASBMB Today?
Become a member to receive the print edition four times a year and the digital edition monthly.
Learn moreGet the latest from ASBMB Today
Enter your email address, and we鈥檒l send you a weekly email with recent articles, interviews and more.
Latest in Science
Science highlights or most popular articles
The science of staying strong
Muscles power every movement, but they also tell the story of aging itself. Scientists are uncovering how strength fades, why some species resist it and what lifestyle and molecular clues could help preserve muscle health for life.
Bacteriophage protein could make queso fresco safer
Researchers characterized the structure and function of PlyP100, a bacteriophage protein that shows promise as a food-safe antimicrobial for preventing Listeria monocytogenes growth in fresh cheeses.
Building the blueprint to block HIV
Wesley Sundquist will present his work on the HIV capsid and revolutionary drug, Lenacapavir, at the ASBMB Annual Meeting, March 7鈥�10, in Maryland.
Gut microbes hijack cancer pathway in high-fat diets
Researchers at the Feinstein Institutes for Medical Research found that a high-fat diet increases ammonia-producing bacteria in the gut microbiome of mice, which in turn disrupts TGF-尾 signaling and promotes colorectal cancer.
Mapping fentanyl鈥檚 cellular footprint
Using a new imaging method, researchers at State University of New York at Buffalo traced fentanyl鈥檚 effects inside brain immune cells, revealing how the drug alters lipid droplets, pointing to new paths for addiction diagnostics.
Designing life鈥檚 building blocks with AI
Tanja Kortemme, a professor at the University of California, San Francisco, will discuss her research using computational biology to engineer proteins at the 2026 ASBMB Annual Meeting.