HSINCHU, Taiwan, Jan. 05, 2026 (GLOBE NEWSWIRE) — Antioxidants have long been regarded as key players in protecting cells and maintaining health, but a research team led by Professor Wen-Ching Wang (王雯靜) from the Department of Life Science at National Tsing Hua University (NTHU) in Taiwan has discovered that glutathione (GSH)—a common antioxidant in the human body—plays a more complex role in cancer cells and may even be a critical factor supporting their survival. The study identifies a key metabolic pathway governing cancer cell viability and proposes a strategy to trigger their self-destruction. The findings were published in the leading international journal Advanced Science, offering a fresh perspective for cancer treatment.
The researchers found that GSH not only helps cells resist oxidative stress but also that it binds to a key metabolic enzyme called pyruvate kinase M2 (PKM2), maintaining it in its most active tetrameric form. PKM2 acts like a switch for cellular energy, directly determining whether cancer cells can rapidly generate energy and biosynthetic precursors to support their continued growth.
Using a driving analogy, Professor Wang explained that when cancer cells lose the protective effect of GSH while being forced to keep PKM2 running at high speed, it’s like facing brake failure and an acceleration surge simultaneously. This dual metabolic stress leads to severe imbalance, excessive lipid peroxidation, and the activation of a self-destruction mechanism known as ferroptosis. In animal experiments, this dual-targeting strategy successfully suppressed tumor growth.
The first author of the study, postdoctoral researcher Tsan-Jan Chen (陳粲然), noted that the activity of enzymes involved in cellular energy metabolism is influenced by highly complex regulatory mechanisms. Through a combination of systematic screenings and structural biology analyses, the team uncovered a previously unknown regulatory mechanism and revealed the potential “dual nature” of antioxidants in cancer cells. In the future, precise manipulation of this metabolic axis could drive cancer cells toward self-destruction under stress, leading to the development of more effective therapeutic strategies.
Through large-scale cancer data analysis, the researchers also identified another key molecule, SLC7A11, which functions as a “logistics hub” for cancer cells by controlling the synthesis and supply of GSH. Higher SLC7A11 expression enables cancer cells to produce greater amounts of GSH and resist ferroptosis, which is strongly associated with increased malignancy and poorer clinical outcomes. Based on these findings, the study proposes the “GSH–PKM2–SLC7A11” metabolic axis as a promising direction for future precision cancer therapies.
The study integrates multiple research approaches, including structural biology, cell experiments, animal tumor models, and large-scale cancer data analysis. Notably, the team successfully resolved the three-dimensional structure of PKM2 bound to GSH, revealing for the first time the operational secrets of a “structural switch” in a key cancer cell protein.
The study won the Rising Star Award at the 19th Conference of the Asian Crystallographic Association (AsCA 2025) and the Glory of Taiwan Award at the 31st Users’ Meeting and Workshops of the National Synchrotron Radiation Research Center. Chen is also the first scholar in Taiwan to earn a double PhD degree from NTHU and Osaka University, highlighting NTHU’s long-term commitment to, and success in, cultivating interdisciplinary research talent who collaborate internationally.
“The double degree program provided a rare opportunity to deeply engage in daily research across different laboratories and access diverse techniques in fields like structural biology and cellular imaging,” said Chen. He added that such training inspired more flexible and multifaceted thinking in his research.
This study represents the outcome of extensive cross-disciplinary, cross-institutional, and international cooperation. The team has long collaborated with Academia Sinica Academician and Taipei Medical University Chair Professor Hsing-Jien Kung (龔行健); Vice President Muh-Hwa Yang (楊慕華) and Associate Professor Chun-Yu Lin (林峻宇) of National Yang Ming Chiao Tung University; Professor Mei-Ling Cheng (鄭美玲) of Chang Gung University; and Professors Yasushi Hiraoka and Tokuko Haraguchi of Osaka University. The collaborators also jointly participate in the T-Star Taiwan Advanced Cancer Research Center Program, supported by Taiwan’s National Science and Technology Council and led by Academia Sinica Academician Mien-Chie Hung (洪明奇), with the shared goal of advancing precision cancer therapy.
Professor Wen-Ching Wang (王雯靜, right) and postdoctoral researcher Tsan-Jan Chen (陳粲然) from NTHU’s Department of Life Science present their latest finding, in which they successfully resolved the three-dimensional structure of pyruvate kinase M2 (PKM2) bound to glutathione (GSH), revealing a key vulnerability in cancer cells. (Photo: National Tsing Hua University, NTHU)
Contact:
Yi-Yeh Chen
National Tsing Hua University, NTHU
(886)3-5162006
[email protected]
A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/198eddec-6125-4863-af31-b1a6d8f92ae1
