Recent studies have elucidated how changes in the chemical structure of proteins called interleukin 6 affect lung cancer growth and response to treatment. Scientists from the National Zheng University and other major institutions have found that in Interleukin 6, abnormal chemical modifications are called defective N-glycosylation, causing cancer cells to spread more easily and resist certain treatments. N-glycosylation refers to the process by which sugar molecules attach to specific sites on a protein, affecting their function. The findings, published in the journal Nature Communications, highlight key factors in how lung cancer develops and is difficult to treat.
Researchers led by Professor Wu-Chou Su and Chun-Hua Hung examine how chemical changes in interleukin 6 affect pathways that control cancer cell behavior. “The way interleukin 6 is chemically modified can help us monitor how lung cancer progresses and is resistant to drugs,” said Professor Su. The study showed that when sugar molecules are added to interleukin 6 at specific sites, it activates a pathway called Janus kinase signaling sensor and transcription 3, thus keeping the cancer under control. This pathway is a series of chemical reactions inside cells that help regulate growth and survival. However, when this chemical change is not occurring, interleukin-6 triggers different pathways, making the cancer more aggressive.
Cancer cells lacking this modification in interleukin 6 show stronger characteristics and can spread to other parts of the body. These cells also resist targeted therapies that typically block cancer growth, such as tyrosine kinase inhibitors, which are drugs designed to interrupt cancer growth signals. Analysis of patient samples confirmed that these resistant cancers had higher levels of abnormally modified interleukin-6, thereby enhancing the link between this defect and drug resistance.
It is worth noting that the study found that this chemically defective interleukin-6 changed the way cancer cells communicate internally. Although modified versions of proteins activate signals for slow cancer growth, defective forms send signals to improve cancer’s ability to move and survive. It activates proteins to make cancer’s proteins, meaning they can grow and spread indefinitely like stem cells. “This signal conversion highlights a new way for new cancers to avoid successful treatment,” Hong said.
These findings have practical implications. Testing specific types of interleukin-6 in patients can help predict whether their cancer will resist treatment. Additionally, new therapies that can prevent the harmful effects of interleukin 6 or return to its normal chemical state can provide better prognosis for patients with lung cancer.
This study breaks through new grounds, which shows that chemical differences in a single protein are small and can greatly alter cancer behavior. It opens the door to innovative therapies targeting these chemical changes and provides hope for addressing drug-resistant lung cancer.
Journal Reference
Chun-Hua Hung, Shanghai-Yin Wu, Cheng-I Daniel Yao et al., “Defective N-glycosylation of IL6 induces metastasis and tyrosine kinase inhibitor resistance in lung cancer.” Nature Communications, 2024. Doi:
About the Author
Professor Wu He is an outstanding expert in medical oncology and is currently an honorary professor in the Department of Oncology at Tanan National Zheng University (NCKU) in Taiwan. He previously held key leadership positions at NCKU, including the Department of Oncology and the Center for Applied Nanomedicine. In addition, he oversaw the Clinical Trial Center, Cancer Center and Department of Internal Medicine at the National Zheng University National Hospital.
Professor SU’s research interests focus on early clinical trials, pathogenesis and treatment of lung cancer, and the role of IL-6/JAK/STAT3 signaling pathway in lung cancer progression. He has also been deeply involved in nanodiagnosis and the development of nanofruits as innovative anti-cancer strategies. Throughout his career, Professor SU has published extensively and has led many clinical trials in the fields of lung cancer and nanomedicine.
Dr. Chun-Hua Hung Her PhD is from the Institute of Basic Medical Sciences, Tanan National Bell (NCKU), Taiwan. She is currently a postdoctoral fellow at NCKU. Her research interests are in tumor biology, focusing on the role of protein glycosylation in cancer metastasis, drug resistance, immunomodulation and spatial cancer biology.
Chun-Hung Lin In 1995, the Scripps Institute received a PhD in chemistry and spent two years postdoctoral training at Harvard Medical School. He then began his independent career in the academic community of Sinica, Taiwan. He has received several awards and honors, including Twas’ young branch (Academies of Sciences in Developing Countries), and the Outstanding Research Award from the National Science and Technology Commission of Taiwan. His research interests are studying carbohydrate-based identification in cancer and infectious diseases, including host-microbial interactions.
Dr. Cheng-i Daniel Yao He received his PhD in Plant Biology from the Arizona State University School of Arts and Sciences. Over the past decade, he has worked in the field of glycosyl mirrors, focusing on glycan purification and analysis and the interaction of coagulans. His research expertise lies in the structural analysis of bacterial glycans and glycolipids related to immune responses in host intestinal immunity.
