Enhanced glucose uptake promotes the survival of hepatocellular carcinoma cells following incomplete radiofrequency ablation.

Abstract

Incomplete radiofrequency ablation (iRFA) exposes residual hepatocellular carcinoma (HCC) cells to sublethal thermal stress, which triggers metabolic adaptations that support cell survival. In this study, we demonstrate that iRFA significantly enhances glucose uptake in HCC cells, contributing to the suppression of intracellular reactive oxygen species (ROS) and promoting cell viability. Mechanistically, this effect is mediated by the translocation of GLUT4 from the cytoplasm to the plasma membrane, rather than changes in total GLUT4 expression. GLUT4 redistribution under thermal stress facilitates rapid glucose uptake, providing energy and biosynthetic intermediates necessary for survival under adverse microenvironmental conditions. Inhibition of GLUT4-mediated glucose uptake increases ROS accumulation and reduces cell survival, highlighting its critical role in redox homeostasis. Collectively, our findings reveal an iRFA-GLUT4-glucose uptake axis as a key metabolic adaptation pathway that enables residual tumor cells to survive sublethal thermal stress, suggesting that targeting GLUT4 dynamics may represent a potential therapeutic strategy to improve the efficacy of iRFA and prevent tumor recurrence.