HSINCHU, Taiwan, Jan. 05, 2026 — While antioxidants are typically recognized for their protective roles in maintaining cell health, 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 uncovered a more complex function for glutathione (GSH), a common antioxidant in the human body, within cancer cells. Their findings suggest GSH may be crucial for cancer cell survival and have identified a key metabolic pathway that governs cancer cell viability, proposing a strategy to induce their self-destruction. These groundbreaking discoveries, published in the esteemed international journal Advanced Science, offer a novel perspective for cancer treatment.
The researchers observed that GSH not only aids cells in resisting oxidative stress but also binds to pyruvate kinase M2 (PKM2), a critical metabolic enzyme. This binding maintains PKM2 in its most active tetrameric form. PKM2 functions as a cellular energy regulator, directly influencing the capacity of cancer cells to rapidly generate energy and biosynthetic precursors essential for their sustained growth.
Professor Wang likened the situation to a car experiencing simultaneous brake failure and an acceleration surge when cancer cells are deprived of GSH’s protective effects while being compelled to maintain high-speed PKM2 activity. This dual metabolic stress results in a severe imbalance, leading to excessive lipid peroxidation and the activation of ferroptosis, a programmed cell death mechanism. In experiments involving animal models, this dual-targeting strategy proved effective in suppressing tumor growth.
Postdoctoral researcher Tsan-Jan Chen (陳粲然), the study’s first author, highlighted the intricate regulatory mechanisms governing enzyme activity in cellular energy metabolism. Through a combination of systematic screenings and structural biology analyses, the team elucidated a previously unknown regulatory mechanism, revealing the potential “dual nature” of antioxidants in cancer cells. The precise manipulation of this metabolic axis in the future could steer cancer cells toward self-destruction under stress, paving the way for more effective therapeutic strategies.
Further analysis of large-scale cancer data by the researchers identified another key molecule, SLC7A11, which acts as a “logistics hub” for cancer cells by regulating GSH synthesis and supply. Elevated SLC7A11 expression allows cancer cells to produce more GSH and resist ferroptosis, a phenomenon strongly correlated with increased malignancy and poorer clinical outcomes. Based on these findings, the study proposes the “GSH–PKM2–SLC7A11” metabolic axis as a promising avenue for future precision cancer therapies.
The study employed a multidisciplinary approach, integrating structural biology, cell experiments, animal tumor models, and large-scale cancer data analysis. Notably, the team successfully determined the three-dimensional structure of PKM2 in complex with GSH, providing the first detailed insight into the operational mechanisms of a “structural switch” within a key cancer cell protein.
The research received 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’s achievement as the first scholar in Taiwan to obtain dual PhD degrees from NTHU and Osaka University underscores NTHU’s dedication to fostering interdisciplinary and internationally collaborative research talent.
“The dual degree program offered an invaluable opportunity to immerse myself in daily research across different laboratories and gain exposure to diverse techniques in fields such as structural biology and cellular imaging,” Chen stated. He added that this training fostered more flexible and multifaceted thinking in his research endeavors.
This study is the result of extensive collaboration across disciplines, institutions, and international borders. The research team has a long-standing partnership with Academia Sinica Academician and Taipei Medical University Chair Professor Hsing-Jien Kung (龔行健); National Yang Ming Chiao Tung University Vice President Muh-Hwa Yang (楊慕華) and Associate Professor Chun-Yu Lin (林峻宇); Chang Gung University Professor Mei-Ling Cheng (鄭美玲); and Osaka University Professors Yasushi Hiraoka and Tokuko Haraguchi. These collaborators are also jointly involved in the T-Star Taiwan Advanced Cancer Research Center Program, supported by Taiwan’s National Science and Technology Council and spearheaded by Academia Sinica Academician Mien-Chie Hung (洪明奇), with the collective aim 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
yiyeh@mx.nthu.edu.tw
