Scientists have discovered a novel mechanism explaining how metabolic changes contribute to liver cancer development, focusing on a specific protein modification that accelerates tumor growth. Researchers from the University of Science and Technology of China found that acetylation of the pyruvate dehydrogenase complex component X (PDHX) plays a crucial role in hepatocellular carcinoma (HCC) progression.
The study reveals that PDHX undergoes acetylation at lysine 488 by the acetyltransferase p300, which disrupts the protein's normal function. This modification impedes the interaction between PDHX and another protein, reducing the pyruvate dehydrogenase complex's activity and redirecting glucose metabolism towards aerobic glycolysis. The metabolic shift results in increased lactate production, which triggers oncogene expression and promotes tumor growth.
Importantly, the researchers discovered that PDHX acetylation is significantly elevated in liver cancer tissues and correlates with poor patient prognosis. When PDHX acetylation was inhibited or PDC activity restored, tumor growth was effectively suppressed. Treatments like dichloroacetate (DCA), which restores PDC function, showed promise in targeting glycolysis-dependent tumors with high PDHX acetylation levels.
The findings suggest PDHX acetylation could serve as a diagnostic biomarker for liver cancer and potentially offer a new therapeutic target. By understanding how metabolic alterations drive cancer progression, researchers can develop more targeted and personalized treatment strategies.
Dr. Huafeng Zhang, a senior study author, emphasized that this research uncovers a new aspect of cancer metabolism, broadening scientific understanding of liver cancer biology and opening promising pathways for therapeutic development.
