Liquid-liquid phase separation: A dynamic driver of hepatocellular carcinoma

Liquid-liquid phase separation (LLPS) is a physicochemical phenomenon prevalent in eukaryotic cells, mediating the compartmentalization of discrete subcellular regions through the formation of membrane-less organelles and biomolecular condensates and thereby enabling precise spatiotemporal regulation of cellular physiological processes. LLPS dysregulation constitutes a pathogenic mechanism underlying various diseases, with accumulating evidence demonstrating its critical involvement in hepatocellular carcinoma (HCC) progression. Here, we summarize the biophysical principles governing LLPS and the biological characteristics of intracellular phase separation, and primarily discuss the mechanistic contributions of aberrant LLPS to HCC pathogenesis, including disrupted gene expression, signal transduction, stress adaptation, etc. We further propose future research directions on LLPS in HCC and highlight its therapeutic potential through pharmacological modulation, aiming to provide novel perspectives for understanding the pathology of HCC and offer new therapeutic targets to facilitate effective strategies for HCC treatment.