Sustainable Development Goals
Abstract/Objectives
Metabolic changes in cancer cells are essential for their rapid proliferation and progression. Under normal conditions, cells utilize aerobic respiration to generate energy. However, even in oxygen-rich conditions, cancer cells tend to rely on glycolysis as their primary metabolic pathway, a phenomenon known as the Warburg Effect. This metabolic shift not only provides energy for cancer cells but also produces essential biomolecules such as DNA, RNA, and proteins needed for cell division, enabling rapid growth. To achieve more sustainable cancer treatments, this research team delved into the metabolic characteristics of cancer cells and discovered that hypoxic conditions in tumors induce the production of hydrogen sulfide (H2S). H2S is a naturally occurring gaseous signaling molecule that modifies the structure and activity of pyruvate kinase PKM2 through protein S-sulfhydration. This promotes cancer cells to absorb more glucose and accelerate proliferation. By blocking the modification of PKM2 by H2S, the team successfully guided cancer cells to restore normal aerobic respiration, cutting off the supply of metabolic intermediates and inhibiting tumor growth in a mouse model of breast cancer. This research, based on interdisciplinary collaboration between metabolic medicine and structural biology, discovers a potential sustainable anti-cancer strategy that avoids reliance on high-dose chemotherapy or radiotherapy, thereby reducing negative impacts on the environment and patients. If this strategy can be further developed into a drug, it could be applied not only to breast cancer treatment but also to sustainable treatments for other types of cancer.
Results/Contributions

Associate Professor Kai-Ti Lin from the Institute of Biotechnology and Associate Professor Cheng Hui-Chun from the Institute of Bioinformatics and Structural Biology at National Tsing Hua University collaborated to unravel the molecular mechanism behind cancer cells' rapid growth. Their research discovered that cancer cells release hydrogen sulfide (H2S), which alters the structure of pyruvate kinase (PKM2), enabling cancer cells to absorb large amounts of glucose, enhance glycolysis, and accelerate tumor proliferation. This groundbreaking finding was published in the international journal Nature Communications.

 

Nearly a century ago, German scientist Otto Warburg discovered that cancer cells prefer glycolysis as their primary metabolic pathway, even in oxygen-rich environments, rather than relying on aerobic respiration to produce energy. This phenomenon, known as the "Warburg Effect," left the question of why cancer cells favor glucose unresolved for decades. Kai-Ti Lin and Hui-Chun Cheng's research revealed that the hypoxic environment within tumors induces the production of hydrogen sulfide. This molecule marks a specific site on PKM2, altering its structure and breaking it down into smaller molecular forms (dimers or monomers), thereby changing the efficiency of glycolysis.

 

The research team used gene-editing technology to block hydrogen sulfide from modifying PKM2. This preserved PKM2's original tetrameric structure, successfully redirecting cancer cells to perform aerobic respiration and inhibiting tumor growth in a breast cancer mouse model. This approach effectively cuts off the supply of intermediates required for cancer cell division, offering a viable strategy for cancer treatment without relying on high doses of chemotherapy.

 

This research combines the fields of metabolic medicine and structural biology, achieving a breakthrough through interdisciplinary collaboration. If further developed into a drug, this method holds great promise for treating breast cancer and other cancers in the future, benefiting countless patients.

Keywords
glucose metabolism, Warburg effect, H2S, cancer
References
Media Information
Contact Information
林愷悌 副教授 / 鄭惠春 副教授
ktlin@life.nthu.edu.tw / hccheng@life.nthu.edu.tw